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  • 1
    Electronic Resource
    Electronic Resource
    Studies on rats fed a dietary fibre preparation from sugar beet (1998)
    Springer
    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 207 (1998), S. 66-73 
    Details
    ISSN: 1431-4630
    Keywords: Key words Dietary fibre ; Sugar beet pulp ; Composition ; Fermentation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Groups of 15 female rats were fed ad libitum for 4 weeks with a standard diet containing 0, 2.5, 5 or 10% of a dietary fibre (DF) preparation made on a laboratory scale from sugar beet pulp. This preparation had a total DF content of 72.2%. Its major components were 36.7% cellulose, 16.9% pectin, 16.8% hemicelluloses (HC) and 11.0% protein. The DF preparation from sugar beet exhibited a water-binding capacity (WBC) of 8.9 g H2O/g. As the proportion of DF preparation in the diet increased, up to 15.8% total DF, 4.6% cellulose and 1.9% pectin were found in the feeds. The WBC of the diets was estimated to be 1.4–2.9 g H2O/g. At the end of the experiment, 20.3–64.1% total DF, 10.3–38.2% cellulose, 0.2–7.8% pectin, 4.3–9.2% HC pentoses and 4.3–10.3% HC hexoses were determined in caecum contents (ca. 0.6 g dry weight/rat). The following proportions were found in faeces (3rd week; 1.4–1.9 g dry weight/rat): 34.5–56.9% total DF, 19.5–36.1% cellulose, 6.4–8.4% HC pentoses, 7.4–8.3% HC hexoses. The WBC of faeces ranged from 3.7 g H2O/g to 4.9 g H2O/g. About 30–50% of the daily intake of DF appeared in the faeces. Higher amounts of total DF, pectin and HC pentoses were fermented by gastrointestinal microflora as the concentration of DF preparation from sugar beet in the diet increased. In addition, the fermentation of different DF components could be shown by the monosaccharide composition of caecum contents and faeces.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002170050296
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  • 2
    Electronic Resource
    Electronic Resource
    Biochemical parameters of rats fed dietary fibre preparation from sugar beet (1998)
    Springer
    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 206 (1998), S. 393-398 
    Details
    ISSN: 1431-4630
    Keywords: Key words Dietary fibre ; Sugar beet pulp ; Biochemical parameters ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Groups of 15 male rats were fed ad libitum for 4 weeks with a standard diet containing 0, 2.5, 5.0 or 10.0% dietary fibre (DF) prepared from sugar beet. The highest food consumption was found in the group with 10% DF in the diet. Food efficiency was highest in the control group. Average body weight increased continuously in all groups without significant differences. Enrichment of the diet with the DF preparation did not substantially influence urinary parameters [pH, specific gravity, protein or activities of aspartate aminotransferase (ASAT), alanine aminopeptidase and alkaline phosphatase (AP)]. Haemoglobin concentration and haematocrit, mean corpuscular haemoglobin concentration and mean corpuscular volume as well as total numbers of erythrocytes, thrombocytes and leukocytes counts did not significantly differ between the groups. Lower counts of eosinophils and neutrophils were measured in rats fed DF-enriched diets. Serum parameters (urea-N, protein, glucose, triglycerides and activities of ASAT, alanine aminotransferase, AP and leucine aminopeptidase) did not differ between groups. As the amount of DF preparation in the diet increased, serum cholesterol was reduced in trend. Furthermore, no significant differences were found between the groups with respect to the organ weights of rats. In conclusion, important or critical dose-related differences in the determined parameters were not found. This sub-acute feeding study showed that no toxic effects were related to used doses of DF which was prepared from sugar beet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002170050280
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  • 3
    Electronic Resource
    Electronic Resource
    Lectin binding patterns in the vomeronasal organ and accessory olfactory bulb of the rat (1998)
    Springer
    Anatomy and embryology 198 (1998), S. 331-339 
    Details
    ISSN: 1432-0568
    Keywords: Key words Accessory olfactory bulb ; Vomeronasal epithelium ; Vomeronasal nerves ; Glycoproteins ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A number of previous studies have indicated that lectin histochemistry is an obvious choice for characterizing the vomeronasal system. However, apparently inconsistent results have been obtained: notably, the affinity with which various lectins bind to the accessory olfactory bulb varies among taxa, even considering closely related species. In the present study, the binding patterns of seven lectins in the rat accessory olfactory bulb, vomeronasal nerves and vomeronasal duct were investigated. The Bandeiraea simplicifolia lectin bound exclusively to the vomeronasal nerve and glomerular layers of the accessory olfactory bulb, while the Ulex europeus and Lycopersicon esculentum lectins bound to these regions and additionally to the nerve and glomerular layers of the main olfactory bulb. Soybean agglutinin showed a similar pattern to that obtained with the Ulex europeus and Lycopersicon esculentum lectins, though it also faintly labelled other parts of the structures examined. The Vicia villosa and Erythrina cristagalli lectins were not specific for the vomeronasal system, since they labelled grey and white matters in structures including the lateral olfactory tract and the anterior olfactory nuclei. The Dolichos biflorus lectin did not bind to vomeronasal tissues. The observed patterns of binding in the accessory olfactory bulb were consistent with those observed in the vomeronasal nerves, but unlike those observed in the epithelium of the vomeronasal duct. This latter result probably reflects binding of lectins to sugar residues contained in secreted mucus rather than those in epithelial nerve endings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050188
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  • 4
    Electronic Resource
    Electronic Resource
    Light and electron microscopic studies of pituitary adenylate cyclase-activating peptide (PACAP) – immunoreactive neurons in the enteric nervous system of rat small and large intestine (1998)
    Springer
    Anatomy and embryology 198 (1998), S. 341-352 
    Details
    ISSN: 1432-0568
    Keywords: Key words Pituitary adenylate cyclase-activating peptide (PACAP) ; Small intestine ; Large intestine ; Enteric nervous system ; Rat ; Immunohistochemistry ; Synapse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Pituitary adenylate cyclase-activating peptide (PACAP)-immunoreactive (IR) neurons in the myenteric and submucosal plexus of the rat small and large intestine were examined by immunostaining with purified polyclonal antiserum against PACAP (1–15), using both light and electron microscopy. Many PACAP-IR neuronal cell bodies and fibers were found in the myenteric and submucosal plexus. Many of the PACAP-IR fibers originated from the cell bodies of the myenteric and submucosal ganglia. The ganglia were also innervated by PACAP-IR fibers. PACAP-IR fibers penetrated both the circular and longitudinal muscle layers, confirming the previous observations indicating that PACAP neurons act as motor neurons. Ultrastructural study demonstrated that PACAP-IR nerve terminals formed synaptic contacts with PACAP-IR nerve cell bodies or dendritic processes. This observation suggests that PACAP-IR neurons innervate other PACAP-IR neurons, and that PACAP neurons work as interneurons in the enteric nervous system. PACAP-IR nerve cells received not only PACAP-positive nerve terminal input also PACAP-negative nerve terminal input. It also suggests that PACAP neurons are regulated not only by PACAP-IR enteric neurons, but also by neurons originating elsewhere. Our observations support the view that PACAP-IR neurons are involved in the control of gut motility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050189
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  • 5
    Electronic Resource
    Electronic Resource
    Behaviour of spermatogonia following recovery from busulfan treatment in the rat (1998)
    Springer
    Anatomy and embryology 198 (1998), S. 53-61 
    Details
    ISSN: 1432-0568
    Keywords: Key words Regenerating spermatogonia ; Asymmetric divisions ; Cytoplasmic bridges ; Busulfan ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study describes the morphological behaviour of spermatogonia following recovery from two doses of busulfan treatment in the rat. Twenty days after the second intraperitoneal injection of busulfan, the testes lost most of their spermatogenic cells and there were fewer dispersed singly surviving spermatogonia. These surviving cells were in close contact with the basal portions of adjacent Sertoli cells and the shrunken basal lamina, and were the source for repopulating the depleted seminiferous epithelium. During the initial stage of repopulation (48 days later), surviving spermatogonia underwent a phase of active proliferation: type A spermatogonia underwent symmetric and asymmetric divisions; type B spermatogonia underwent asynchronous differentiation. At day 96, normal spermatogenesis was fully recovered in many seminiferous tubules, represented by 80% of the rats regaining various degrees of fertility at day 120. These data provide an additional model for the study of self-renewal of stem spermatogonia and suggest that the asymmetric division of type A spermatogonia and their close contact with both the basal lamina and the Sertoli cells may be involved in regulating the number of stem spermatogonia and the delicate process of normal spermatogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050164
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  • 6
    Electronic Resource
    Electronic Resource
    Visual zone of the claustrum shows localizational and organizational differences among rat, guinea pig, rabbit and cat (1998)
    Springer
    Anatomy and embryology 198 (1998), S. 63-72 
    Details
    ISSN: 1432-0568
    Keywords: Key words Claustrum ; Visual cortex ; Visual zones Comparative anatomy ; Rat ; Guinea pig ; Rabbit ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The retrograde axonal transport method was used to compare the topography and organization of the visual zone of the claustrum in rat, guinea pig, rabbit and cat. First, massive Fluoro-Gold injections were placed into the primary visual cortex and the secondary areas. Experiments showed differences in the location of the visual zone among the animals under study. In rat, the visual zone occupied the posteroventral part of the claustrum and spread to its anterior pole. In guinea pig, neurons projecting to the visual cortex were located dorsally in the posterior half of the claustrum. In rabbit, similarly to the rat, they were localized in the posteroventral part; however, they did not reach the anterior pole. In cat, neurons that project to the visual cortex were concentrated dorsally in the posterior fourth of the claustrum. In double-injection experiments, Fast Blue and Diamidino Yellow were placed into the primary and secondary visual areas in various combinations. The experiments showed that in the rat and the rabbit claustral neurons project to primary visual cortex (area 17) as well as to both secondary visual areas (areas 18a and b). Populations of neurons sending axons to the primary and secondary areas showed full overlap. The presence of double-labeled neurons indicates that some claustral neurons project both to the primary and secondary fields. In cat, neurons that project to the primary visual cortex appear to be clearly separated from those connected with the secondary visual area, as no double-labeled neurons were found. In all studied species, the double injections placed into the visual and primary somatosensory cortex did not result in any double-labeling neurons. Our results indicate that the location of the visual zone in the posterior part of the claustrum is a phylogenetically stable feature, whereas its dorsoventral shift as well as the extent toward the anterior pole is related to the particular species. The overlap of neurons projecting to the primary and secondary visual areas in the rat and rabbit as well as the separation of both projections in cat appear to reflect the higher degree of complexity of the visual system in the latter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050165
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  • 7
    Electronic Resource
    Electronic Resource
    Evidence for transformation of chondrocytes and site-specific resorption during the degradation of Meckel’s cartilage (1998)
    Springer
    Anatomy and embryology 197 (1998), S. 439-450 
    Details
    ISSN: 1432-0568
    Keywords: Key words Meckel’s cartilage ; Chondrocyte ; Transformation ; Resorption ; Apoptosis ; Mouse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is unknown whether cells in the midportion of Meckel’s cartilage undergo transformation into other kinds of cell or whether resorption of cells occurs during development. Therefore, the midportion of Meckel’s cartilage from the mouse and the rat was subdivided into anterior and posterior portions. The ultimate fates of these tissues were analyzed with a focus on resorption-related cells, death of chondrocytes by apoptosis, and transformation of the chondrocytes themselves. Cellular and extracellular features of mouse Meckel’s cartilage were observed after von Kossa’s staining and staining for acid phosphatase (APase) activity, as well as by light and electron microscopy. To identify resorbing cells, immunostaining specific for macrophages and staining for tartrate-resistant acid phosphatase (TRAP) were performed. The DNA nick end-labeling (TUNEL) method was used for the detection of death of chondrocytes by apoptosis. The replacement of the extracellular matrix of rat Meckel’s cartilage was examined with double immunofluorescence staining for type I and type II collagens. When the anterior midportion from embryonic mice on day 18 was examined after von Kossa’s staining, it was clear that the extracellular matrix had already calcified and vascularization had been initiated that reflected the calcified matrix. TRAP staining and immunostaining for macrophages revealed two types of osteoclast and macrophages that were involved in resorption of the matrix. In the posterior midportion, no vascular invasion was evident, and chondrocytes were transformed directly into fibroblastic cells by phenotypic conversion. In such cells we found reaction products specific for APase activity, suggestive of the intracellular degradation of fine collagenous fibrils. Double immunofluorescence staining showed that cartilage-specific type II collagen was replaced by type I collagen with the phenotypic transformation to fibroblastic cells. There were no significant changes in the number of TUNEL-positive apoptotic cells from day 17 of gestation to day 6 after parturition. Death of chondrocytes by apoptosis was not, therefore, involved directly in the disappearance of Meckel’s cartilage. These results in the posterior midportion served as an instance of phenotypic switches in differentiated cells from chondrocytes to fibroblast-like cells. The present study indicates that there is a difference between the ultimate fate of cells in the posterior part and that of cells in the anterior part in the midportion of Meckel’s cartilage in the mouse and rat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004290050155
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  • 8
    Electronic Resource
    Electronic Resource
    Structural organization of rat CD1 typifies evolutionarily conserved CD1D class genes (1998)
    Springer
    Immunogenetics 48 (1998), S. 22-31 
    Details
    ISSN: 1432-1211
    Keywords: Key words CD1 ; Rat ; Gene ; Organization ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The non-major histocompatibility complex (MHC)-encoded CD1 family has recently emerged as a new antigen-presenting system that is distinct from either MHC class I or class II molecules. In the present study, we determined the genomic structure of the rat CD1 locus. It was extremely similar to mouse CD1 genes, especially to CD1D1. The 5′ flanking region of the CD1 gene contained the binding motifs for two cytokine-inducible transcription factors, NF-IL2-A and NF-IL6. Some regulatory elements found in MHC class I genes (enhancer A, enhancer B, and the IFN response element) were absent. It is of interest that a tyrosine-based motif for endosomal localization found in the human CD1b cytoplasmic tail was encoded by a single short exon which was conserved in all CD1 molecules except for CD1a. Southern blot and direct sequencing analyses of inbred rat strains suggested very limited polymorphism in the 5′ region where a hydrophobic ligand-binding groove is encoded; a single base substitution resulted in amino acid alteration of alanine (GCT) to valine (GTT) at codon 119. Comparison of the overall exon-intron organization of CD1 genes revealed that the length of the intron was also characteristic to each of the two classes of CD1 genes, classic CD1 and CD1D; such categorization has hitherto been made according to the sequence similarity of the coding region. This finding provides further support for the hypothesis that the two classes have different evolutionary histories. In contrast to the complete absence of the classic CD1 in rats and mice, the entire region of nonpolymorphic CD1D has been conserved through mammalian evolution. Similar functional properties of rodent CD1 and human CD1d are implied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050396
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  • 9
    Electronic Resource
    Electronic Resource
    Lung overinflation without positive end-expiratory pressure promotes bacteremia after experimental Klebsiella pneumoniae inoculation (1998)
    Springer
    Intensive care medicine 24 (1998), S. 172-177 
    Details
    ISSN: 1432-1238
    Keywords: Key wordsK. pneumoniae ; Bacteremia ; Mechanical ventilation ; Blood gases ; Animal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine the effect of peak inspiratory pressure (PIP) and positive end-expiratory pressure (PEEP) on the development of bacteremia with Klebsiella pneumoniae after mechanical ventilation of intratracheally inoculated rats. Design: Prospective, randomized, animal study. Setting: Experimental intensive care unit of a University. Subjects: Eighty male Sprague Dawley rats. Interventions: Intratracheal inoculation with 100 μl of saline containing 3.5–5.0 × 105 colony forming units (CFUs) K. pneumoniae/ml. Pressure-controlled ventilation (frequency 30 bpm; I/E ratio = 1 : 2; FIO2 = 1.0) for 180 min at the following settings (PIP/PEEP in cmH2O): 13/3 (n = 16); 13/0 (n = 16); 30/10 (n = 16) and 30/0 (n = 16), starting 22 h after inoculation. Arterial blood samples were obtained and cultured before and 180 min after mechanical ventilation and immediately before sacrifice in two groups of non-ventilated control animals (n = 8 per group). After sacrifice, the lungs were homogenized to determine the number of CFUs K. pneumoniae. Measurements and results: The number of CFUs recovered from the lungs was comparable in all experimental groups. After 180 min, 11 animals had positive blood cultures for K. pneumoniae in group 30/0, whereas only 2, 0 and 2 animals were positive in 13/3, 13/0 and 30/10, respectively (p 〈 0.05 group 30/0 versus all other groups). Conclusions: These data show that 3 h of mechanical ventilation with a PIP of 30 cmH2O without PEEP in rats promotes bacteremia with K. pneumoniae. The use of 10 cmH2O PEEP at such PIP reduces ventilation-induced K. pneumoniae bacteremia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340050541
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  • 10
    Electronic Resource
    Electronic Resource
    Renal vascular hyperresponsiveness to elevated ionized calcium in spontaneously hypertensive rat kidneys (1998)
    Springer
    Intensive care medicine 24 (1998), S. 61-70 
    Details
    ISSN: 1432-1238
    Keywords: Key words Blood vessels ; Kidney ; Renal circulation ; Renal vascular resistance ; Calcium ; Ionized calcium ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: Calcium may be indicated in critically ill patients for hemodynamic support. Its well-known action includes peripheral vasoconstriction. Vascular effects of calcium are unknown, however, in the presence of hypertension or in combination with calcium channel blocking drugs, commonly prescribed in the treatment of hypertension. The renal vessels of the spontaneously hypertensive rat (SHR) represent a suitable study model, because their vascular reactivity closely agrees with that in hypertensive humans. The present study should clarify (a) are the renal vessels of SHR responsive to high and low ionized calcium ([Ca++] within the clinical ranges? (b) because release of nitric oxide is calcium ion dependent, are renal vascular responses altered after inhibition of NO synthase? (c) are vascular responses of SHR to hypercalcemia altered by the calcium channel blocking drug verapamil? Animals and interventions: We compared isolated kidneys of SHR and those of two strains of age-matched normotensive rats (NTR) in their responses to high and low [Ca++]. They were perfused with oxygenated, warmed (37 °C) albumin containing Krebs-Henseleit buffer. In protocol A (n = 8 for each rat strain) steady state high [Ca++] (1.88 mmol/l) and low [Ca++] (0.55 mmol/l) were instituted in randomized order. In protocol B (n = 8 for each rat strain) interventions identical to those of protocol A were instituted after inhibition of NO synthase with NG monomethyl-L-arginine (L-NMMA). In protocol C, high and low [Ca++] levels were instituted in SHR after verapamil pretreatment. At each [Ca++] we measured changes in renal flow at constant perfusion pressures of 100 and 150 mm Hg. Results: In SHR (perfusion pressure 100 mm Hg), high [Ca++] induced a decrease in renal flow (–11.8 ± 1.8 % of control), which was significantly greater (p 〈 0.05) than the change (− 6.1 ± 1.5 and − 6.9 ± 1.4 % of control) recorded in the two normotensive strains. In SHR (perfusion pressure 150 mmHg), high [Ca++] induced a decrease in renal flow (− 12 ± 1.3 % of control), also significantly greater (p 〈 0.05) than the changes (− 6.2 ± 1.1 and −5.8 ± 1.7 % of control) in the two normotensive strains. Similar differences and significances were again observed after L-NMMA pretreatment. In SHR, verapamil prevented renal vascular responses in SHR to both high and low [Ca++]. Conclusions: First, renal vascular responses to high [Ca++] in SHR are exaggerated. At the upper end of the hypercalcemia range the observed changes in renal flow at constant perfusion pressure were modest, however, and with lesser degrees of hypercalcemia they may be anticipated to be even less pronounced. Second, effects of high [Ca++] were abolished after verapamil. If these findings are clinically applicable, they are of interest when calcium is infused in patients with hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340050516
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  • 11
    Electronic Resource
    Electronic Resource
    Structural organization, sequence analysis, and physical mapping of the Grc-linked class Ib gene RT1.S3 in the rat (1998)
    Springer
    Immunogenetics 48 (1998), S. 76-81 
    Details
    ISSN: 1432-1211
    Keywords: Key words RT1.S3 ; Grc ; MHC ; Class I ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050405
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  • 12
    Electronic Resource
    Electronic Resource
    Reduction of thyroid hormone levels by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats (1998)
    Springer
    Archives of toxicology 72 (1998), S. 541-544 
    Details
    ISSN: 1432-0738
    Keywords: Key words Polychlorinated biphenyl ; Methylsulfonyl metabolite ; Total thyroxine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Sprague-Dawley rats received four consecutive intraperitoneal doses of four kinds of methylsulfonyl (MeSO2) metabolites of polychlorinated biphenyl (PCB) congeners: 3-MeSO2-2,2′,3′,4′,5,6-hexachlorobiphenyl (3-MeSO2-CB132); 3-MeSO2-2,2′,3′,4′, 5,5′-hexachlorobiphenyl (3-MeSO2-CB141); 3-MeSO2-2,2′,4′,5,5′,6-hexachlorobiphenyl (3-MeSO2-CB149) and 4-MeSO2-2,2′,4′,5,5′,6-hexachlorobiphenyl (4-MeSO2-CB149). The congeners were major MeSO2-PCBs determined in human milk, liver and adipose tissue, and the aim was to determine their effect on thyroid hormone levels. All four tested MeSO2 metabolites (20 μmol/kg once daily for 4 days) reduced serum total thyroxine levels by 22–44% at a much lower dose than phenobarbital (PB; 431 μmol/kg once daily for 4 days) on days 2, 3, 4 and 7 after the final doses. Total triiodothyronine levels were reduced 37% by treatment with 4-MeSO2-CB149 at day 7. A 30% increase in thyroid weight was produced by 3-MeSO2-CB141 treatment. Total cytochrome P450 content was increased by 3-MeSO2-CB132, 3-MeSO2-CB141 and 3-MeSO2-CB149, but not by 4-MeSO2-CB149. Thus, it is likely that the 3-MeSO2-hexachlorobiphenyls and 4-MeSO2-CB149 could influence the thyroid hormone metabolism by different mechanism(s). The results show that tested 3- and 4-MeSO2 metabolites of PCB congeners reduce thyroid hormone levels much more than PB in rats. Our finding suggests that the metabolites may act as endocrine-disrupters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050540
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  • 13
    Electronic Resource
    Electronic Resource
    Arsenobetaine is not a major metabolite of arsine gas in the rat (1998)
    Springer
    Archives of toxicology 72 (1998), S. 706-710 
    Details
    ISSN: 1432-0738
    Keywords: Keywords Arsine gas ; Metabolism ; Arsenobetaine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Many organisms can easily dispose of toxic inorganic arsenic species through gradual methylation of the element and further urinary excretion. In order to clarify the urinary excretion of arsenobetaine observed in a human case of intoxication by arsine, the capacity of highly methylated arsenical synthesis has been investigated in rats acutely exposed during 1 h to increasing concentrations of the same gas [4 to 80 mg AsH3/m3]. Urinary metabolites of arsenic were determined with good agreement in two (Belgian and Italian) laboratories using two different analytical procedures. The sum of inorganic, mono- and dimethylated metabolites of arsenic in urine was shown to be related to the intensity of exposure to arsine. A biphasic relationship was observed: 1 h exposure to 〉60 mg AsH3/m3 led to metabolite excretion which is roughly 10 times higher than for exposure levels below that limit, suggesting the saturation of a binding site reserve and the availability for metabolism of a greater proportion of the As absorbed above this threshold. Arsenobetaine production, if any, could only be detected when its presence in food was excluded; in addition, amounts appeared negligible and could be disregarded as a common arsenic metabolite in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050564
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  • 14
    Electronic Resource
    Electronic Resource
    Induction by mercury compounds of brain metallothionein in rats: Hg0 exposure induces long-lived brain metallothionein (1998)
    Springer
    Archives of toxicology 72 (1998), S. 187-191 
    Details
    ISSN: 1432-0738
    Keywords: Key words Methylmercury ; Mercury vapor ; Metallothionein ; Brain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Metallothionein (MT) is one of the stress proteins which can easily be induced by various kind of heavy metals. However, MT in the brain is difficult to induce because of blood-brain barrier impermeability to␣most heavy metals. In this paper, we have attempted to induce brain MT in rats by exposure to methylmercury (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood-brain barrier and cause neurological damage. Rats treated with MeHg (40 μmol/kg per day × 5 days, p.o.) showed brain Hg levels as high as 18 μg/g with slight neurological signs 10␣days after final administration, but brain MT levels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7–8 μg Hg/g brain tissue 24 h after cessation of exposure. At that time brain MT levels were about twice the control levels. Although brain Hg levels fell gradually with a half-life of 26 days, MT levels induced by Hg exposure remained unchanged for 〉2␣weeks. Gel fractionation revealed that most Hg was in the brain cytosol fraction and thus bound to MT. Hybridization analysis showed that, despite a significant increase in MT-I and -II mRNA in brain, MT-III mRNA was less affected. Although significant Hg accumulation and MT induction were observed also in kidney and liver of Hg vapor-exposed rats, these decreased more quickly than in brain. The long-lived MT in brain might at least partly be accounted for by longer half-life of Hg accumulated there. The present results showed that exposure to Hg vapor might be a suitable procedure to provide an in vivo model with enhanced brain MT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050486
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  • 15
    Electronic Resource
    Electronic Resource
    Involvement of the locus coeruleus in analgesic effects of a low dose of naloxone during the inflammatory process (1998)
    Springer
    Experimental brain research 119 (1998), S. 166-170 
    Details
    ISSN: 1432-1106
    Keywords: Key words Locus coeruleus ; Analgesia ; Inflammation ; Naloxone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We evaluated the effects of systemic administration of a low dose of naloxone in rats with bilateral lesions in the area of the locus coeruleus (LC) under conditions of unilateral inflammation, compared with those in sham-operated rats. In each group, rats received a single s.c. injection of carrageenan (6 mg in 0.15 ml saline), and effects of a low dose of naloxone (5 μg/kg, i.p.) on thermal nociception were examined at 4 h and 7 days following the induction of unilateral hindpaw inflammation. The antinociceptive effect was assessed by prolongation of the paw withdrawal latency (PWL) to noxious thermal stimuli. Prior to induction of inflammation, the low dose of naloxone had no significant effect on PWLs in either the sham-operated or the LC-lesioned rats. Four hours after carrageenan injection, the low dose of naloxone produced prolongation of PWLs in the sham-operated rats but failed to induce antinociception in the LC-lesioned rats. Antinociceptive effects were observed in both groups of rats 7 days after carrageenan injection. These results suggest that the LC is involved in naloxone-induced antinociception during the early phase of inflammation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050330
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  • 16
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    Neuropeptide FF in the lateral spinal and lateral cervical nuclei: Evidence of contacts on spinothalamic neurons (1998)
    Springer
    Experimental brain research 119 (1998), S. 159-165 
    Details
    ISSN: 1432-1106
    Keywords: Key words Neuropeptide FF ; Spinothalamic neurons ; Lateral cervical nucleus ; Lateral spinal nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Neuropeptide FF (NPFF, F8Famide) is best known for its modulating effect on opioid analgesia and morphine tolerance. However, the exact mode of action of NPFF in sensory transmission is not known. We compared the distribution of NPFF-immunoreactive (ir) fibers and terminal-like thickenings with the retrograde, tracer-filled spinothalamic (ST) neurons in the lateral spinal nucleus (LSN) and lateral cervical nucleus (LCN) of rat, areas where NPFF-containing nerve terminals are abundant. We injected fluorescent latex microspheres into the ventroposterolateral thalamic nucleus and more medial thalamic nuclei, which are innervated by ST neurons. We found NPFF-ir terminal-like thickenings and fibers apposing the tracer-filled neurons in the LSN and LCN. ST neurons filled with the retrograde tracer making contacts with NPFF-ir terminal-like thickenings, were found to terminate not only in the ventroposterolateral thalamic nucleus but also in more medial thalamic nuclei. The highest number of tracer-filled ST neurons having NPFF-ir terminal-like thickenings and fibers in apposition were found at the cervical level. Our results suggest that NPFF-containing systems in the spinal cord of rat are not limited to the substantia gelatinosa, and the sensory functions of NPFF may be mediated at least partly through the modulation of the ST system. NPFF-ir contacts in the LSN and LCN might play an important role in the somatic sensory transmission system. This study shows evidence for the first time that the spinal NPFF-containing system may be involved in mechanisms that control sensory input to the supraspinal levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050329
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  • 17
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    Changes in the mRNA expression pattern, with special reference to calcitonin gene-related peptide, after axonal injuries in rat motoneurons depends on age and type of injury (1998)
    Springer
    Experimental brain research 119 (1998), S. 191-204 
    Details
    ISSN: 1432-1106
    Keywords: Key words Growth-associated protein-43 ; Galanin ; c-jun ; Low-affinity nerve growth factor receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The axotomy reaction in motoneurons after a peripheral nerve transection in the adult animal is characterized by a robust upregulation of alpha-calcitonin gene-related peptide (CGRP) messenger RNA (mRNA) together with mRNAs encoding cytoskeletal and growth-related proteins. Here we have examined whether the nature of the lesion and the age of the animal have any impact on the mRNA regulation in severed cells. Thus, the effect of a sciatic nerve transection in the adult rat was compared with, on the one hand, ventral root avulsions in the adult animal and, on the other hand, sciatic nerve transection in the immature animal. In the two latter cases, a proportion of the lesioned cells die and overall chances of regeneration are small. In the adult animal a sciatic nerve transection induced an upregulation of alpha-CGRP mRNA from the 3rd day after surgery and throughout the first 3 weeks (the time span of the study). Also low-affinity nerve growth factor receptor (p75) and growth-associated protein-43 (GAP-43) mRNAs were upregulated during the entire 3-week period. In contrast, after ventral root avulsion, the expression of alpha-CGRP, c-jun, and p75 mRNAs were normalized within the 1st postoperative week, while GAP-43 mRNA was still upregulated at 3 weeks. Galanin message-associated peptide (GMAP) mRNA became upregulated preferentially in motoneurons subjected to ventral root avulsion, while nitric oxide synthase (NOS) mRNA was expressed exclusively after the latter type of injury. In the immature animal, alpha-CGRP mRNA was downregulated after sciatic nerve transection in rats aged 3 days or 7 days at the time of surgery; while, in contrast, an upregulation was seen in 12- or 21-day-old animals. GAP-43 and c-jun mRNAs were upregulated in lesioned motoneurons of all ages, while GMAP mRNA was upregulated preferentially in lesioned motoneurons of early postnatal animals. p75 mRNA was expressed in unlesioned immature motoneurons until the age of 7–10 days. The downregulation of p75 mRNA in intact cells at this age coincided with a developmental switch in the ability of axotomized cells to express increased levels of p75 mRNA. No expression of NOS mRNA was detectable in lesioned cells of any of the age groups. These results show that the age of the animal and the type of axonal injury are indeed to a high degree influencing the changes seen in the protein expression pattern in axotomized rat motoneurons. The different responses in these paradigms suggest differences in the trophic response from surrounding glia or the trophic responsiveness of lesioned motoneurons. Also, the results may indicate different roles for the studied substances during the regenerative response of lesioned neurons. Of the substances studied here, upregulation of alpha-CGRP and p75 mRNAs best correlated with a possibility of axon regeneration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050333
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  • 18
    Electronic Resource
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    Group III metabotropic glutamate receptor agonists modulate high voltage-activated Ca2+ currents in pyramidal neurons of the adult rat (1998)
    Springer
    Experimental brain research 119 (1998), S. 237-244 
    Details
    ISSN: 1432-1106
    Keywords: Key words Calcium conductances ; l-2-Amino-4-phosphonobutyrate ; l-Serine-O-phosphate ; Neuroprotection ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In pyramidal neurons of the rat sensorimotor cortex, we have investigated the modulation of high voltage-activated calcium currents by agonists at group III metabotropic glutamate receptors (mGluRs). l-2-Amino-4-phosphonobutyrate (l-AP4) and l-serine-O-phosphate (l-SOP) reduced calcium currents in the vast majority of cells isolated from the adult animal. Interestingly, this modulation was negligible in the young animals (2–14 postnatal days), becoming prominent only after full development (more than 21 days). The efficacy of l-SOP mimicked l-AP4 in reducing calcium currents. Yet, l-SOP produced saturating responses at about 3 μM and significant modulation at nanomolar concentrations (EC50=923 nM). The voltage-dependence of the group III mGluR-mediated responses was evaluated by comparing the inhibition of “standard” and “facilitated” conductances. On the calcium currents facilitated by depolarizing prepulse, 3 μM l-SOP produced a mean 13.4% inhibition compared with 19.6% in control condition, supporting the proposition that part of the modulation was voltage-dependent. The calcium current inhibition caused by the activation of group III metabotropic glutamate receptors was only partially sensitive to ω-conotoxin GVIA, but largely inhibited by ω-agatoxin IVA, at concentrations (100 nM) known to block P- and Q-type channels. Conversely, the dihydropyridine antagonists nifedipine and nimodipine (50–500 nM) failed to prevent the group III mGluR-mediated response in the majority of tested cells (more than 65%). Furthermore, the long-lasting tail promoted by the inclusion of the dihydropyridine agonist Bay K 8644 was not consistently affected by l-SOP and l-AP4. These findings imply that the observed modulation involves different channel subtypes, namely N- and P- or Q-type channels, and suggests that group III mGluRs play an important role in the intrinsic and synaptic functions of adult cortical pyramidal neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050337
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  • 19
    Electronic Resource
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    Effects of noradrenaline on rate-level function of auditory cortex neurons: Is there a “gating” effect of noradrenaline? (1998)
    Springer
    Experimental brain research 118 (1998), S. 361-372 
    Details
    ISSN: 1432-1106
    Keywords: Key words Noradrenaline ; Neuromodulator ; Iontophoresis ; Intensity function ; Threshold ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To test a potential “gating” effect of noradrenaline (NA) in the auditory cortex, the acoustic threshold was estimated by determining the rate-level function of neurons before, during, and after microiontophoretic application (5–40 nA) of NA. The rationale behind this experiment was that a gating effect should decrease the threshold for acoustic excitatory responses. From 84 recorded neurons, we observed (1) that application of NA increased the threshold for 48 of 84 cells, and (2) that, on average, the slope of the rate-level functions was unchanged. These effects on the threshold are consistent with the fact that the dominant effect of NA on the evoked response is inhibition for 34 of 84 cells; increases in evoked responses were observed for only 14 of 84 cells. GABA application (0–50 nA) also led to increased response threshold for 19 of 24 cells (unaffected, 5 of 24 cells). However, for three cells the effect of GABA application was antagonized by bicuculline application, while on the same cells bicuculline application did not prevent the noradrenergic increase in threshold. The effect induced by NA on the threshold raises questions about the generality of a gating effect of NA in sensory neocortex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050290
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  • 20
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    Effects of macrophage migration inhibitory factor and macrophage migration stimulatory factor on function and survival of foetal dopaminergic grafts in the 6-hydroxydopamine rat model of Parkinson′s disease (1998)
    Springer
    Experimental brain research 120 (1998), S. 95-103 
    Details
    ISSN: 1432-1106
    Keywords: Key words Brain transplantation ; MIF ; MSF ; 6-OHDA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Activated microglia play an important role in the rejection of intracerebral grafts and the degeneration of axotomized neurones. We studied the effect of macrophage migration stimulatory factor (MSF) or macrophage migration inhibitory factor (MIF) on allogeneic foetal mesencephalic dopaminergic grafts transplanted into the striatum of 6-hydroxydopamine-lesioned rats. Rotation testing revealed a significant compensation of lesion-induced motor asymmetry 3 weeks post-grafting in animals treated with MIF and vehicle-treated controls compared with pre-graft values (Student′s t-test, P≤0.005) and MSF-treated animals (ANOVA, post hoc Fisher PLSD test, P≤0.05). The MSF group showed no significant compensation. Graft recipients with MIF application (1452.06 ± 164.32 tyrosine hydroxylase-positive ventral mesencephalic cells) and controls (1753.21 ± 165.51 tyrosine hydroxylase-positive neurones) displayed good graft survival. Animals with MSF application showed a significant reduction of tyrosine hydroxylase-positive grafted cells (MSF 570.36 ± 209.49 cells) and graft volumes compared with the MIF and the control group (ANOVA, post hoc Fisher PLSD test, P≤0.05). The propotional area of microglia was significantly reduced in MIF animals compared with control animals (ANOVA, post hoc Fisher PLSD test, P≤0.001). Activated microglia and macrophages were reduced by half in the MIF-treated group compared with MSF animals and controls. We conclude that intrastriatal injections of MSF result in impaired function and survival of allogeneic ventral mesencephalon (VM) grafts 3 weeks after transplantation. MIF can reduce the number of microglia and macrophages in allogeneic foetal VM grafts. A reduction of microglia via MIF application did not enhance graft function and survival.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050381
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  • 21
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    Electronic Resource
    NOS-like immunoreactive neurons express GABA-like immunoreactivity in rabbit and rat retinae (1998)
    Springer
    Experimental brain research 120 (1998), S. 109-113 
    Details
    ISSN: 1432-1106
    Keywords: Key words Nitric oxide synthase ; GABA ; Retina ; Rabbit ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In rabbit and rat retinae, wholemounted preparations and 40 μm thick vibratome sections were processed for nitric oxide synthase (NOS) immunoreactivity and consecutive semithin sections were immunostained with anti-NOS and anti-GABA antisera, respectively. Two types of NOS-labelled amacrine cells were identified: type 1 cells with larger somata were intensely stained, and type 2 cells with smaller somata were weakly stained. A few displaced amacrine cells also showed NOS-like immunoreactivity. All these NOS-like immunoreactive neurons also expressed GABA-like immunoreactivity. Thus, nitric-oxide-containing neurons might constitute a subpopulation of GABAergic neurons in rabbit and rat retinae.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050383
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  • 22
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    Behavioral asymmetries and neurochemical changes after unilateral lesions of tuberomammillary nucleus or substantia nigra (1998)
    Springer
    Experimental brain research 120 (1998), S. 273-282 
    Details
    ISSN: 1432-1106
    Keywords: Key words Basal ganglia ; Hippocampus ; Tectum ; Dopamine ; Serotonin ; Histamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies in the rat have shown that the hypothalamic tuberomammillary nucleus, the major source of neuronal histamine, is related to mechanisms of learning, memory, reinforcement, and functional recovery. These functional relationships were found to be partly lateralized. Therefore, we decided to analyze whether unilateral ibotenic acid lesions aimed at this brain region would acutely lead to asymmetries in open-field behavior, and whether they would affect the biogenic amines dopamine and serotonin in the neostriatum, hippocampus, and tectum. We compared this manipulation with unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta and with unilateral ibotenic acid lesions of the substantia nigra pars reticulata. These lesions were investigated because all three brain areas are anatomically linked to the neostriatum, are related to the neurotransmitters dopamine and serotonin, and play a role in behavioral asymmetry and functional recovery. In support of previous findings, our data show that 6-hydroxydopamine lesions of the substantia nigra pars compacta led to an ipsiversive asymmetry in turning and scanning. Ibotenic acid lesions of the adjacent pars reticulata led to contraversive turning, whereas thigmotactic scanning was reduced bilaterally. In contrast, ibotenic acid lesions of the tuberomammillary nucleus did not affect turning, but led to an ipsilateral asymmetry in scanning. Neurochemically, the 6-hydroxydopamine lesion was mainly characterized by the well-known ipsilateral neostriatal dopamine depletion and increased residual dopamine activity. In hippocampus and tectum, these transmitters were not specifically affected, except for an asymmetry of serotonin in the superior colliculus. The ibotenic acid lesions of the pars reticulata did not deplete neostriatal dopamine, indicating that they spared the dopaminergic output of the substantia nigra. In contrast, they affected dopaminergic and serotonergic measures in the colliculi, which may be due to damage of the nigral GABAergic projection to this brain area. In animals with unilateral ibotenic acid lesions of the tuberomammillary nucleus, several markers of dopaminergic and serotonergic acitivity were increased in the neostriatum, tectum, and hippocampus. This effect may have been due to the loss of inhibition otherwise provided by the wide-ranging histaminergic output of the tuberomammillary nucleus. These results are discussed with respect to the major outputs of the three brain areas, their potential impacts on neurotransmitters in their projection sites, and their role in behavioral asymmetry.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050401
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  • 23
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    Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter I. Evidence from chronaxie measurements (1998)
    Springer
    Experimental brain research 118 (1998), S. 477-488 
    Details
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Brain slice ; Strength-duration relations ; Conduction velocity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Extracellular electrical stimulation of the gray matter is often used to determine the function of a given cortical area or pathway. However, when it is used to elicit postsynaptic effects, the presynaptic neuronal elements activated by electrical stimulation have never been clearly identified: it could be the excitable dendrites, the cell body, the axon initial segment, or the axonal branches. To identify these elements, we performed two series of experiments on slices of rat visual cortex maintained in vitro. The first series of experiments, reported in this paper, was aimed at determining the chronaxie, a temporal parameter related to the membrane properties of the neuronal elements. In order to identify the presynaptic elements that were activated by extracellular electrical stimulation, chronaxies corresponding to postsynaptic responses were measured and compared with those corresponding to the activation of axons (antidromic activation) and those corresponding to the activation of cell bodies (intracellular current injection in intracellularly recorded neurons). The chronaxie for orthodromic activation was similar to that for axonal activation, but was 40 times smaller than the chronaxie for direct cell body activation. This suggests that, whenever a postsynaptic response is elicited after electrical stimulation of the cortical gray matter, axons (either axonal branches or axon initial segments), but not cell bodies, are the neuronal elements activated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050304
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  • 24
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    Inflammation-induced increase in the density of neuropeptide-immunoreactive nerve endings in rat skeletal muscle (1998)
    Springer
    Experimental brain research 121 (1998), S. 174-180 
    Details
    ISSN: 1432-1106
    Keywords: Key words Substance P ; Nerve growth factor ; Growth-associated protein 43 ; Nerve endings ; Myositis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The density of substance P (SP)-, calcitonin gene-related peptide (CGRP)- and vasoactive intestinal polypeptide (VIP)-immunoreactive (ir) nerve endings was quantitatively evaluated in intact and inflamed gastrocnemius-soleus muscle of the rat. In persistently inflamed muscle (12 days after a single injection of Freund’s adjuvant into the muscle), the density of SP-ir fibres was significantly increased. CGRP- and VIP-ir fibres displayed an insignificant increase in density. The density of fibres ir for nerve growth factor (NGF) and for growth-associated protein 43 (GAP-43/B-50), a marker for axonal sprouting, regeneration and synaptic reorganisation, increased significantly in persistently inflamed muscle. The data are consistent with the established contribution of NGF on the expression of SP and GAP-43 in afferent neurones under the influence of a persistent inflammation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050449
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  • 25
    Electronic Resource
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    Modulation of sensory inhibition in the ventrobasal thalamus via activation of group II metabotropic glutamate receptors by 2R,4R-aminopyrrolidine-2,4-dicarboxylate (1998)
    Springer
    Experimental brain research 121 (1998), S. 181-185 
    Details
    ISSN: 1432-1106
    Keywords: Key words Metabotropic glutamate receptors ; 2R ; 4R-4-Aminopyrrolidine-2 ; 4-dicarboxylate ; Somatosensory thalamus ; Presynaptic inhibition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recordings were made from single neurones responsive to somatosensory input in the ventrobasal thalamus of the anaesthetised rat. GABAergic afferent inhibition arising from the thalamic reticular nucleus was evoked using a condition-test vibrissal stimulation paradigm. Local iontophoretic application of the group II metabotropic glutamate receptor (mGluR) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) in the vicinity of the recorded neurones produced a reduction of the afferent inhibition (from 78±3.0% to 25±5.3%), presumably via a presynaptic mechanism. This effect could be antagonised by LY307452, a known group II mGluR antagonist. In contrast, two selective group I mGluR agonists, (S)-3,5-dihydroxyphenylglycine (DHPG) and trans-azetidine-2,4-dicarboxylate (tADA), were without effect on the GABAergic inhibition. These data show that group II but not group I mGluRs can have a significant role in the modulation of GABAergic afferent inhibition in the ventrobasal thalamus. This could be of importance in the control of sensory discriminative processes and functions of sleep, arousal and seizure generation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050450
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  • 26
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    Environmental enrichment alters organizational features of the forepaw representation in the primary somatosensory cortex of adult rats (1998)
    Springer
    Experimental brain research 121 (1998), S. 191-204 
    Details
    ISSN: 1432-1106
    Keywords: Key words Primary somatosensory cortex ; Forepaw skin map ; Environmental enrichment ; Cortical plasticity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The cortical forepaw area of young adult rats was mapped by recording the response properties of small clusters of neurons in layer IV of the primary somatosensory (SI) cortex. First we quantitatively analyzed the somatotopic organizational features of the cortical forepaw representation in terms of areal extent and topography, receptive field (RF) sensory modality, size, and location. We also assessed the influence of environmental enrichment, known to induce structural alterations in cortical connectivity, on the representational characteristics of the forepaw maps. Long-Evans rats were housed in environments (standard, SE; enriched, EE) promoting differential tactile experience for 71–113 days from weaning. Within the SI, we found a single and complete topographic map of the cutaneous surfaces of the forepaw consisting of a rostrolateral-caudomedial sequence of digit and pad representational zones. Small islets of noncutaneous responses (NCR; high-threshold, deep-receptor input) within the boundaries of the cutaneous maps were a conspicuous feature of the forepaw map for SE rats. These islets created discontinuities in the representation of contiguous skin territories. In the SE rats, about 79% of the cortical sites activated by light tactile stimulation had a single cutaneous RF, whereas about 21% exhibited multiple RFs. Most single-digit RFs we delineated in the SE rats extended across two or three phalanges. As a result, the representations of the phalangeal skin surfaces were not segregated but formed an overlapping continuum. Moreover, within these regions, as the electrode was displaced in regular steps across the mediolateral axis, RFs did not shift across the digit skin surface in an orderly manner, suggesting a lack of internal topography in the finger representation zones. Tactile experience promoted by environmental enrichment induced alterations in the representational features of the SI cutaneous map of the forepaw. In EE rats, the areal extent of the forepaw cutaneous representation was 1.5 times larger than in SE rats. Indeed, the cutaneous map extended into NCR cortical sectors along its external margins and also into NCR islets found in the forepaw area. Consequently, in EE rats there were fewer representational discontinuities. The areal enlargement was due to a selective increase in the areal extent of the glabrous but not the hairy skin surface representations. Furthermore, protuberant glabrous skin (digit tips, palmar pads) was represented over larger cortical regions than were other glabrous skin territories less likely to be stimulated during object palpation and manipulation. Maps from EE rats were also characterized by a larger proportion of sites with single RFs (88% compared with 79%). In addition, glabrous RFs from EE rats were smaller and more clustered on the digit tips and palmar pads than were RFs in SE rat maps. RF size on hairy skin surfaces remained unchanged. Because the RFs were smaller, the cutaneous maps of EE rats contained distinct representations of digit phalangeal glabrous skin. RFs tended to exhibit more orderliness in their progression across the digit glabrous skin of EE rats than they did in SE rats. The phalanges of EE rats were represented in distinct patches. Neurons in EE rats were more sensitive to light tactile stimulation than were neurons in SE rats. These alterations were presumably mediated by the selective potentiation of cutaneous over deep-receptor activation. More generally, the present study corroborates the view that cortical cutaneous maps are maintained in a permanent state of use-dependent fluctuation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050452
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  • 27
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    Changes in the extracellular levels of glutamate and aspartate during ischemia and hypoglycemia Effects of hypothermia (1998)
    Springer
    Experimental brain research 121 (1998), S. 277-284 
    Details
    ISSN: 1432-1106
    Keywords: Key words Hypoglycemia ; Hypothermia ; Microdialysis ; Ischemia ; Transmitter release ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Hypothermia (33° C) dramatically diminishes ischemic but not hypoglycemic brain damage. The beneficial effects of hypothermia in ischemia have been partly attributed to a reduction in the ischemia-induced increase in synaptic levels of glutamate or aspartate. With the microdialysis technique, we studied the effects of hypothermia (33° C) on the brain extracellular levels of glutamate and aspartate during hypoglycemia, ischemia, and their combination. In isoelectric hypoglycemia, striatal levels of glutamate and aspartate frequently show large transients of transmitter release occurring during both normothermia and hypothermia, whereas in the cortex levels of glutamate and aspartate are slightly lower during hypothermia compared with normothermia. In both regions studied, complete ischemia induced by i.v. KCl results in a progressive increase in glutamate and aspartate levels over time. In normoglycemic animals, hypothermia markedly attenuates the increase in glutamate and aspartate levels in the striatum but not in the cortex. Also in hypoglycemic animals, complete ischemia causes a progressive increase in the glutamate and aspartate levels. However, hypothermia affects only striatal glutamate levels. Since hypothermia protects both cortex and striatum against ischemic brain injury and not against hypoglycemic injury, presumably the protective effect of hypothermia is due to factors other than prevention of glutamate or aspartate overflow.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050461
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  • 28
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    Time-course expression of vascular endothelial growth factor as related to the development of the retinochoroidal vasculature in rats (1998)
    Springer
    Experimental brain research 118 (1998), S. 155-160 
    Details
    ISSN: 1432-1106
    Keywords: Key words Retinochoroidal vasculature ; Retinal pigment epithelium ; Vascular endothelial growth factor ; In situ hybridization ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Growth factors involved in angiogenesis are critical to both the normal and pathological vascular development in the retina and choroid. In the present experiment, the relationship between the vascular endothelial growth factor (VEGF) expression and the retinochoroidal vasculogenesis in Sprague-Dawley rats was investigated using in situ hybridization and immunohistochemistry. It was found that VEGF was produced mainly by astrocytes and Müller cells in the neural retina, and this was correlated temporally and spatially with the retinal vasculogenesis. In addition, it was observed that, although the VEGF expression in the retinal pigment epithelium (RPE) decreased with increasing age, it persisted from the embryonic stage to adulthood. These findings indicate that the VEGF expression in RPE may play a role in the development of the choroidal vessels as well as in the maintenance of the normal structure and permeability of the choriocapillaris in adults.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050267
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  • 29
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    Ascending propriospinal afferents to area X (substantia grisea centralis) of the spinal cord in the rat (1998)
    Springer
    Experimental brain research 119 (1998), S. 356-366 
    Details
    ISSN: 1432-1106
    Keywords: Key words Spinal cord ; Central canal ; Substantia grisea centralis ; Propriospinal afferents ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Area X (the tenth area) of the spinal cord is a region surrounding the central canal and extending throughout the spinal cord length. Using anterograde and retrograde labeling techniques, ascending propriospinal projections to area X were examined in the rat. For anterograde tracing of axons, biotinylated dextran was injected into middle-thoracic, lumbar, or sacral-caudal segments. Unilateral injections resulted in bilateral labeling of terminals in area X of all segments rostral to the injections. The distribution of labeled terminals was conspicuous in regions dorsal and lateral to the central canal. The labeled axons were derived from the ventrolateral and the lateral cord. They coursed through lamina VII, giving off terminal axons. While giving off terminal axons in area X, they coursed further rostrally or caudally along the central canal or crossed over the central canal to terminate in the contralateral area X. Possible cells of origin of these ascending afferents were examined after injections of wheat germ agglutinin-horseradish peroxidase into regions surrounding the central canal (area X) at the cervical or thoracic level. Retrogradely labeled neurons were consistently seen in area X, and laminae VII and VIII of the thoracic and lumbar segments. The present study shows that ascending propriospinal axons project to area X of all spinal levels rostral to the cells of origin and suggests that some of these afferents may originate from neurons in area X and laminae VII and VIII. Based on previous data, it is surmised that area X functions, through these intricate interconnections, as a site for integration or modulation of somatic or nociceptive and visceroceptive sensation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050351
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    Do non-dopaminergic neurons in the ventral tegmental area play a role in the responses elicited in A10 dopaminergic neurons by electrical stimulation of the prefrontal cortex? (1998)
    Springer
    Experimental brain research 118 (1998), S. 466-476 
    Details
    ISSN: 1432-1106
    Keywords: Key words Extracellular recording ; Cortical efferents ; A10 cell group ; Non-dopaminergic neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is rapidly becoming apparent that the prefrontal cortex (PFC) plays a major role in controlling the activity of midbrain dopaminergic (DA) neurons. We have previously demonstrated that electrical stimulation of the PFC elicits inhibition-excitation (IE) and excitation (E) activity patterns in DA neurons in the ventral tegmental area (VTA; A10 cell group). Since non-DA neurons in the VTA are cortically innervated, synapse upon DA neurons and appear to have an inhibitory impact, we determined the extent to which the responses of these neurons to stimulation of the PFC could account for the responses seen in DA neurons upon cortical stimulation. Stimulation of the PFC (0.25 mA and 1.0 mA) elicited three categories of response in the majority of VTA non-DA neurons. Types I and II were characterised by a short-to-moderate latency excitation (referred to as “early excitations”), in the latter case preceded by inhibition. Type III responses consisted of inhibition in the absence of an early excitation. Elements of these responses were compared with the temporal characteristics of key elements of responses elicited in DA neurons by PFC stimulation. Although the early excitations in non-DA neurons preceded the inhibitions in DA neurons exhibiting IE responses, the early excitations began approximately 100 ms before the inhibitions in DA neurons and often ended several tens of milliseconds before the inhibitions began, making a causal relationship between these events unlikely. The inhibitions in Type III responses, combined with the inhibitions which followed the early excitations in many Type I and II responses, showed temporal characteristics that suggested a possible causal relationship with the excitations in DA neurons exhibiting E responses, but not those exhibiting IE responses. However, since the excitatory phases of E and IE responses appear to be homologous, the lack of involvement of non-DA neurons in the excitatory phase of IE responses tends to cast doubt on the involvement of non-DA neurons in the excitation during E responses. In fact, the most coherent impression that emerges is that non-DA neurons in the VTA do not influence the activity of A10 DA neurons on a short time-scale (i.e. phasically), but instead may influence activity on a longer time-scale (i.e. tonically).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050303
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    Comparison of sympathetic sprouting in sensory ganglia in three animal models of neuropathic pain (1998)
    Springer
    Experimental brain research 120 (1998), S. 432-438 
    Details
    ISSN: 1432-1106
    Keywords: Key words Causalgia ; Hyperalgesia ; Mechanical allodynia ; Peripheral nerve injury ; Sympathetically maintained pain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Sympathetic postganglionic fibers sprout in the dorsal root ganglion (DRG) after peripheral nerve injury. Therefore, one possible contributing factor of sympathetic dependency of neuropathic pain is the extent of sympathetic sprouting in the DRG after peripheral nerve injury. The present study compared the extent of sympathetic sprouting in the DRG as well as in the injured peripheral nerve in three rat neuropathic pain models: (1) the chronic constriction injury model (CCI); (2) the partial sciatic nerve ligation injury model (PSI); and (3) the segmental spinal nerve ligation injury model (SSI). All three methods of peripheral nerve injury produced behavioral signs of ongoing and evoked pain with some differences in the magnitude of each pain component. The density of sympathetic fibers in the DRG was significantly higher at all examined postoperative times than controls in the SSI model, while it was somewhat higher than controls only at the last examined postoperative time (20 weeks) in the CCI and PSI models. Therefore, data suggest that, although sympathetic changes in the DRG may contribute to neuropathic pain syndromes in the SSI model, other mechanisms seem to be more important in the CCI and PSI models at early times following peripheral nerve injury.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050416
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    Influence of hypoglycemic coma on brain water and osmolality (1998)
    Springer
    Experimental brain research 120 (1998), S. 461-469 
    Details
    ISSN: 1432-1106
    Keywords: Key words Hypoglycemic coma ; Specific gravity ; Brain edema ; Tissue osmolality ; Blood-brain barrier permeability ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To study the effects of pronounced hypoglycemia on brain osmolality and brain edema formation, fasted rats were rendered hypoglycemic by injection of insulin, and subjected to 30 min of hypoglycemic coma. Recovery was accomplished by glucose administration. The change in water content in different brain regions was measured as a change in specific gravity after 30 min of hypoglycemic coma, or 30, 60, and 180 min after glucose administration. Plasma and brain tissue osmolality were measured in separate animals. The results show a significant decrease in specific gravity (increase in water content) in all structures measured (caudoputamen, neocortex, hippocampus, and cerebellum) at the end of the period of coma, as well as after 30 min and 60 min of recovery. At 180 min of recovery, brain water was normalized. The edema affected all structures to the same degree regardless of their vulnerability to hypoglycemic damage. Brain tissue osmolality showed a tendency to decrease with decreasing tissue glucose content. The decrease was significant (P〈0.01) at 30 min of isoelectric coma. In the recovery phase, normal brain osmolality was restored within 30 min. Measurements of blood-brain barrier (BBB) permeability after 30 min of hypoglycemic coma showed no extravasation of Evan’s blue, though a small but significant increase in the permeability for aminoisobutyric acid (AIB) in caudoputamen and in cerebellum was found. To analyze the importance of tissue acidosis for formation of edema, hypoglycemic animals were made acidotic by increasing the CO2 concentration in inspired air to produce an arterial plasma pH of 6.8–6.9. In these animals the edema was of a similar degree to the normocapnic animals, and the permeability for AIB was normal. We conclude that osmolytic mechanisms are not the primary cause of the selective neuronal vulnerability in hypoglycemic coma. Furthermore, the BBB is largely intact during a hypoglycemic insult.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050419
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    Calcium metabolism of focal and penumbral tissues in rats subjected to transient middle cerebral artery occlusion (1998)
    Springer
    Experimental brain research 120 (1998), S. 503-509 
    Details
    ISSN: 1432-1106
    Keywords: Key words Extracellular calcium concentration ; Total tissue calcium content ; Middle cerebral artery occlusion ; Reperfusion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present experiments were undertaken to define changes in tissue calcium metabolism in focal and perifocal (“penumbral”) tissues following 2 h of transient middle cerebral artery occlusion (MCAO) in rats, induced with an intraluminal filament occlusion technique. The extracellular calcium concentration ([Ca2+]e) was measured with ion-selective microelectrodes in neocortical focus and penumbra. For measurement of total tissue calcium content, tissue samples from these areas were collected and analyzed with atomic absorption spectrometry. During MCAO, [Ca2+]e in a neocortical focal area fell from a normal value of about 1.2 mM to values around 0.1 mM, suggesting translocation of virtually all extracellular calcium to intracellular fluids. Recirculation was accompanied by re-extrusion of calcium within 5–7 min; however, [Ca2+]e never returned to normal but stabilized at about 50% of the control value for the first 6 h, and decreased further after 24 h. In penumbral areas, [Ca2+]e showed the expected transient decreases associated with spreading depression-like (or ischemic) depolarization waves. Recirculation was followed by return of [Ca2+]e towards normal values. In the focus, water content increased from about 79% to about 80.4% at the end of the 2-h period of ischemia. After 2 h and 4 h of recirculation, the edema was aggravated (mean values 81.9% and 81.2%, respectively). After 6 h and 24 h, the edema was more pronounced (83.6% and 83.8%, respectively). In the penumbra, no significant edema was observed until 6 h and 24 h of recirculation. The total tissue calcium content in the focus (expressed by unit dry weight) increased at the end of the ischemia period demonstrating calcium translocation from blood to tissue. After 6 h and 24 h, the content increased two- to threefold, compared with control. Changes in the penumbra were qualitatively similar but less pronounced, and a significant increase was not observed until after 6 h of recirculation. The results suggest that 2 h of MCAO leads to a profound perturbation of cell calcium metabolism. In focal areas, cells fail to extrude the calcium that is gradually accumulated during reperfusion and show massive calcium overload after the first 4–6 h of recirculation. Penumbral tissues show a similar increase in calcium concentration after 6 h of recirculation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050424
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    Calbindin D28K and parvalbumin gene expression in rat embryonic ventral forebrain grafts (1998)
    Springer
    Experimental brain research 118 (1998), S. 551-563 
    Details
    ISSN: 1432-1106
    Keywords: Key words: Transplantation ; Calbindin D28K ; Parvalbumin ; Septum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study characterizes expression of calbindin D28 K (CB-D28 K) and parvalbumin (PV) in ventral forebrain (VFB) grafts placed in the neocortex of adult rats bearing quisqualic acid lesions to the nucleus basalis magnocellularis. Three to nine months after transplantation surgery, rats were killed for in situ hybridization with probes to CB-D28K or PV and for immunohistochemistry with antibodies to CB-D28K or PV. In addition, an antibody to choline acetyltransferase (ChAT) was used to characterize the cholinergic component in the graft and an antibody to tyrosine hydroxylase (TH) to explore catecholaminergic innervation of the graft. Quantitative analysis of CB-D28K and PV messenger ribonucleic acid (mRNA) was based on counts of silver grains generated by emulsion autoradiography. Cells expressing CB-D28K mRNA were significantly larger than such cells in the adult VFB and the mean number of silver grains per cell was significantly greater than to such cells in the adult VFB. The level of CB-D28K mRNA expression as calculated by ratio of silver grains per unit area was also significantly increased. Quantification of PV mRNA showed no significant differences between the cells in the graft and in the adult VFB. In order to begin to interpret these findings, a comparison was made with such cells in the VFB of developing rats. Brain sections were sampled from embryonic day 17 and postnatal days 1, 5, 12, 19 and adult (6–12 months of age). Cells expressing CB-D28K mRNA were detected in ventral forebrain from postnatal day 5 and cells expressing PV mRNA were detected in ventral forebrain from postnatal day 19. In the course of normal development of the ventral forebrain, no CB-D28K cells were found that were as large or expressed such high levels of CB-D28K mRNA as observed in the grafts. We conclude that changes in grafted cells expressing CB-D28K do not reflect an arrest of developmental processes. TH immunohistochemistry revealed lack of catecholaminergic innervation of the graft, whereas adult mediolateral septal cells that express CB-D28K receive such innervation in addition to other neurotransmitter inputs. Imbalance in neurotransmitter inputs to grafted cells expressing CB-D28K is discussed as a possible factor in their increased size and gene expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050311
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    Modulation of mRNA expression of the neurotrophins of the nerve growth factor family and their receptors in the septum and hippocampus of rats after transient postnatal thyroxine treatment I. Expression of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin 4 mRNA (1998)
    Springer
    Experimental brain research 119 (1998), S. 1-8 
    Details
    ISSN: 1432-1106
    Keywords: Key words Thyroid hormone ; Neurotrophins ; Septum ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Early postnatal application of thyroid hormones to rats results in morphological changes in septum and hippocampus. Modulation in the expression of either neurotrophins and/or their receptors is postulated to be responsible for these effects. In the present study we tested whether thyroxine administration leads to changes in the expression of neurotrophins of the nerve growth factor (NGF) family. Newborn rats were treated daily with subcutaneous injections of thyroxine until postnatal day (P) 12 at maximum. The pups were killed at defined intervals from P2 to 21. The septal area and the hippocampi were analyzed using the reverse transcriptase-PCR method for quantitation of NGF, brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 messenger RNA (mRNA) levels. In hippocampus of hyperthyroid rats, as compared to controls, we found higher levels of BDNF and NT-3 mRNA over the total investigation period, whereas in the septum a thyroxine-dependent increase in NT-3 mRNA expression was observed. In addition, significant thyroxine-induced effects were found for all variables (except for NGF in the septum) at particular postnatal days. From these data we conclude that modulation of neurotrophin expression is a possible mechanism for the morphological modifications within the hippocampal mossy fiber system and the septohippocampal cholinergic system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050313
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    Activation of the ornithine decarboxylase-polyamine system and induction of c-fos and p53 expression in relation to excitotoxic neuronal apoptosis in normal and microencephalic rats (1998)
    Springer
    Experimental brain research 120 (1998), S. 519-526 
    Details
    ISSN: 1432-1106
    Keywords: Key words Oncogene expression ; Polyamines ; Neuropathology ; Apoptosis ; Olfactory cortex ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Microencephalic rats obtained by gestational treatment with the DNA alkylating agent methylazoxymethanol, show a remarkable lack of sensitivity to excitotoxic neuropathology caused by systemic injections of the convulsant neurotoxin kainic acid. Taking advantage of this, we have studied in these rats, as well as in normal rats, the relationship between the induction of cellular signals supposedly related to cell death and the neuronal apoptosis consequent to kainic acid administration. While normal rats responded to the excitatory insult with a large and relatively long lasting increase of the activity of the enzyme ornithine decarboxylase and of the concentration of putrescine in some brain regions, these alterations were much smaller in microencephalic rats. Expression of c-fos in brain regions sensitive to kainic acid was quicker but lasted a noticeably shorter time in microencephalic rats as compared to normal animals. A profusion of apoptotic neurons, labeled by an in situ technique, were observed in the olfactory cortex, amygdala and hippocampus of normal rats injected with kainic acid, in particular 48 h and 72 h after drug administration. At corresponding time intervals and with similar topographic localization, neurons expressing p53 protein were observed. By contrast, microencephalic rats displayed only in a few cases and in a small number apoptotic neurons in restricted areas of the ventral hippocampus and entorhinal cortex. Noticeably, in these cases small populations of p53-expressing neurons were also present in the same areas. The present observations clearly show that oncogenes such as c-fos and p53, as well as ornithine decarboxylase which behaves as an immediate-early gene in the brain under certain circumstances, undergo noticeably lower and/or shorter induction in microencephalic rats exposed to excitotoxic stimuli. In these rats, therefore, the cellular signalling pathways studied here and related to excitotoxic sensitivity and committment to cell death are downregulated as a probable consequence of altered brain wiring.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050426
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    Posttraining epinephrine and memory consolidation in rats with different basic learning capacities The role of the stria terminalis (1998)
    Springer
    Experimental brain research 121 (1998), S. 20-28 
    Details
    ISSN: 1432-1106
    Keywords: Key words Stria terminalis ; Epinephrine ; Memory consolidation ; Two-way active avoidance ; Basic learning capacities ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rats received bilateral stria terminalis (ST) lesions or were sham-operated. Five days later, the animals were trained in a two-way active avoidance task (one session, 30 trials) and, immediately after the training session, received 0.01 mg/kg i.p. epinephrine or distilled water. Retention was tested 20 days after the acquisition session. In sham-operated groups, epinephrine improved retention in rats that were poor learners and impaired it in rats that were good learners. In poor learners with posttraining epinephrine, lesions of the ST not only blocked the facilitatory effect of epinephrine but also disrupted performance throughout the retention session. In good learners, ST lesions attenuated the disruptive effect of epinephrine. Lesions per se did not affect either acquisition or retention. We conclude that ST is involved in the modulatory effect of posttraining epinephrine on memory consolidation. In addition and considering the results observed in rats that were poor learners, we suggest that emotional factors and/or other amygdaloid pathways different from the ST could participate in the effects of posttraining epinephrine, along with the ST.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050432
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    Monotherapy with dextromethorphan or tirilazad – but not a combination of both – improves outcome after transient focal cerebral ischemia in rats (1998)
    Springer
    Experimental brain research 122 (1998), S. 121-127 
    Details
    ISSN: 1432-1106
    Keywords: Key words Dextromethorphan ; Tirilazad mesylate ; Combination drug therapy ; Cerebral ischemia ; Cerebral blood flow ; Neuroprotection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cell death after cerebral ischemia is mediated by a massive release of excitatory amino acids, generation of free radicals, and – a crucial step – calcium influx into cells. We examined the hypothesis that concurrent administration of drugs ameliorating brain damage via different mechanisms would result in a synergistic neuroprotective effect. The neuroprotective efficacy of two clinically available drugs – the N-methyl-d-aspartate and calcium-channel antagonist dextromethorphan (DM) and the antioxidant tirilazad – were studied in monotherapy and in combination in a rat model of transient focal ischemia. Male Sprague-Dawley rats were subjected to 90 min of middle-cerebral-artery occlusion by an intraluminal filament technique. The animals were randomly assigned to one of four treatments (n=10 each): (1) vehicle-treated controls, (2) DM, (3) tirilazad, (4) DM+tirilazad. Drugs or vehicles were administered 15 min before ischemia and at reperfusion. Local cerebral blood flow (LCBF) was bilaterally recorded by continuous laser Doppler flowmetry. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed planimetrically after 7 days. DM prevented post-ischemic hypoperfusion. Tirilazad did not influence LCBF. Monotherapy with DM or tirilazad improved neurological function and reduced infarct volume by 45% and 48%, respectively. Combination therapy failed to influence neurological recovery and infarct volume. Although, from pharmacological point of view, a synergistic neuroprotective effect is expected, combination of dextromethorphan and tirilazad may lead to mutual inhibition or potentiate adverse effects.
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    URL: http://dx.doi.org/10.1007/s002210050498
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    Opioid inhibition of rat medial vestibular nucleus neurones in vitro and its dependence on age (1998)
    Springer
    Experimental brain research 122 (1998), S. 196-202 
    Details
    ISSN: 1432-1106
    Keywords: Key words Opioid ; Enkephalin ; Medial vestibular nucleus ; Age ; In vitro ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Extracellular and whole-cell patch clamp intracellular recordings were made from rat medial vestibular nucleus (MVN) neurones in vitro, and their responses to selective μ-, κ- and δ-opioid receptor agonists and antagonists were examined. Of 127 neurones tested, the large majority were inhibited in a dose-dependent manner by the δ-opioid receptor agonists [d-Ala2, d-Leu5]-enkephalin (DADLE) and [d-Pen2, Pen5]-enkephalin (DPLPE). The μ-opioid receptor agonist morphine and the κ-receptor agonist U50,488 did not affect the tonic discharge rate of any of the 63 MVN cells tested. The δ-receptor antagonist naltrindole effectively antagonised the inhibitory effects of DADLE and DPLPE. Weak excitatory responses to high doses of DADLE were seen in only two MVN cells. These results demonstrate the presence of δ- but not μ- or κ-opioid receptors on tonically active MVN neurones. Whole-cell intracellular recordings from MVN cells in a current clamp showed that the DADLE-induced inhibition was accompanied by membrane hyperpolarisation and decrease in input resistance, while voltage clamp experiments showed that DADLE induced an outward membrane current that was reduced but not abolished by 20 mM tetraethylammonium bromide. Thus the mechanisms of action of DADLE in inhibiting MVN cells involve the potentiation of outward K currents, in a similar way to the effects of opioids in other areas of brain. The inhibitory effects of DADLE increased linearly with age, so that the responses to DADLE in the youngest animals used here (60–80 g, approx. 3 weeks of age) were relatively small, increasing significantly over the following 2–3 weeks. This age-dependence may be due to post-natal changes in the density of δ-opiate receptors or the efficacy of the signalling pathways activated by them in the MVN cells over this time.
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    URL: http://dx.doi.org/10.1007/s002210050507
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    Evidence that spinal endogenous opioidergic systems control the expression of chronic pain-related behaviors in spinally injured rats (1998)
    Springer
    Experimental brain research 118 (1998), S. 259-268 
    Details
    ISSN: 1432-1106
    Keywords: Key words Central pain ; Endogenous opioids ; Naloxone ; Neuropathic pain ; Spinal cord ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously reported that ischemic spinal cord injury in rats leads to chronic pain-related behaviors. Thus, rats exhibited aversive reactions to innocuous mechanical stimuli (mechanical allodynia) applied to a body area at or rostral to the dermatomes innervated by the injured spinal segments. The responses of the rats to cold are also markedly enhanced (cold allodynia). Interestingly, more than 50% of spinally injured rats did not develop these abnormal pain-related behaviors after spinal cord injury. In the present study, we showed that the extent of injury is similar between allodynic and nonallodynic rats. Furthermore, intrathecal (i.t.) naloxone, a broad-spectrum opioid receptor antagonist, reversibly provoked mechanical and cold allodynia-like responses in spinally injured rats that did not develop such behaviors spontaneously. However, naloxone did not elicit such reactions in normal rats and did not alter the tail-flick latency in normal or spinally injured rats. Furthermore, i.t. d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) or naltridole, selective antagonists of μ and δ opioid receptors, respectively, also triggered pain-related behaviors similarly to naloxone. Although norbinaltorphimine (nor-BIN), a selective κ-receptor antagonist, also elicited such responses, the time course of the effect makes it unlikely that spinal κ-receptors were involved. These results suggested that the expression of abnormal pain-related behaviors in some spinally injured rats is tonically suppressed by the spinal opioidergic system. Interindividual differences that lead to lack or dysfunction of such inhibition may underly the appearence of pain-related behavior in some, but not all, spinally injured rats. It is suggested that such inhibition is exerted through spinal μ and δ, but not κ, opioid receptors. The endogenous opioidergic control appears to be only active against abnormal pain-related behaviors in spinally injured rats. Our results are relevant for the clinical observation that only a subgroup of patients with nerve injury suffers from neuropathic pain.
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    URL: http://dx.doi.org/10.1007/s002210050280
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    On the cutaneous receptors contributing to withdrawal reflex pathways in the decerebrate spinal rat (1998)
    Springer
    Experimental brain research 118 (1998), S. 71-77 
    Details
    ISSN: 1432-1106
    Keywords: Key words Pain ; Nociception ; Analgesia ; Flexion reflex ; Spinal cord ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies indicate that the withdrawal reflex system in the rat has a “modular” organization, each reflex pathway performing a specific sensorimotor transformation. Here, we wished to clarify which cutaneous receptors contribute to this system and to determine whether there are differences in this respect between reflex pathways of different muscles. Withdrawal reflexes of the peroneus longus, extensor digitorum longus, and semitendinosus muscles were recorded with EMG techniques during high reflex excitability in decerebrate spinal rats (n=26). While maintained innocuous pressure on glabrous skin could elicit a sustained reflex activity in all muscles studied, vibration of glabrous skin (10–300 Hz) always failed to evoke a reflex response, suggesting that slowly adapting, but not rapidly adapting, low-threshold mechanoreceptive fibers from this type of skin contribute to withdrawal reflex pathways. Thermal stimulation in the innocuous range, i.e., cooling from 32 to 17°C, or warming the skin from 32 to 41°C, always failed to produce reflex responses, indicating that neither cold nor warm receptors contribute to withdrawal reflex pathways. When either cooling or warming the skin to the noxious temperatures of 1°C or above 45°C, respectively, a reflex discharge was often evoked in the muscles studied. Intradermal administration of histamine, a potent pruritogenic substance, produced very weak, or no, reflex response. In contrast, mustard oil produced vigorous reflex responses in all muscles studied. These findings suggest that some chemonociceptors contribute only weakly, or not at all, to withdrawal reflex pathways. The present data suggest that a selective set of cutaneous receptors contribute to withdrawal reflex pathways and that different withdrawal reflex pathways receive input from essentially the same cutaneous receptor types.
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    URL: http://dx.doi.org/10.1007/s002210050256
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    Depletion of calcitonin gene-related peptide from the caudal trigeminal nucleus of the rat after electrical stimulation of the Gasserian ganglion (1998)
    Springer
    Experimental brain research 118 (1998), S. 111-114 
    Details
    ISSN: 1432-1106
    Keywords: Key words Caudal trigeminal nucleus ; Calcitonin generelated peptide ; Migraine ; Trigeminal ganglion ; Electrical stimulation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Electrical stimulation of the Gasserian ganglion resulted in partial depletion of calcitonin gene-related peptide (CGRP) from ipsilateral central terminals of pseudounipolar primary sensory ganglion cells. Affected terminals exhibit decreased CGRP immunoreactivity as shown by cytophotometric densitomery of the caudal trigeminal nucleus. The decrease in CGRP immunoreactivity is statistically significant only in the medial one-third of the caudal trigeminal nucleus. Since earlier studies have shown that electrical stimulation of the Gasserian ganglion induces first accumulation then depletion of CGRP from perivascular sensory terminals in the dura mater, the present experiments suggest that CGRP is depleted also from central terminals of primary sensory trigeminal neurons, which might be of importance in the pathogenesis of migraine headache.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050260
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    The corticostriatal system mediates the “paradoxical” contraversive rotation but not the striatal hyperexpression of Fos induced by amphetamine early after 6-hydroxydopamine lesion of the nigrostriatal pathway (1998)
    Springer
    Experimental brain research 120 (1998), S. 153-163 
    Details
    ISSN: 1432-1106
    Keywords: Key words Amphetamine ; Fos ; Rotational behavior ; Corticostriatal afferents ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In rats with unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway, amphetamine produces ipsiversive rotational behavior and activation of Fos in the intact striatum, but practically no activation of Fos in the denervated striatum. However, a seemingly paradoxical contraversive rotation, accompanied by intense striatal Fos activation in the lesioned striatum, has been observed during the first few days postlesion. In the present work, behavioral tests and immunohistochemistry for Fos protein and tyrosine hydroxylase (TH) were combined to study striatal changes 36 h after 6-OHDA lesion and particularly the possible involvement of glutamatergic corticostriatal afferents. Injection of amphetamine (0.5 mg/kg or 5 mg/kg) induced contraversive rotation and strong and evenly distributed Fos expression in the lesioned striatum; in the contralateral striatum, however, Fos density was lower than in nonlesioned rats. Pretreatment with the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 (either 0.5 mg/kg or 5 mg/kg) did not significantly affect the hyperexpression of Fos in the lesioned striatum, but suppressed the contraversive rotation. Similarly, rats that were subjected to corticostriatal deafferentation (confirmed by sensory neglect tests) and 6-OHDA lesion (1 week or 3 weeks later) showed no significant reduction in the striatal Fos hyperexpression induced by amphetamine (0.5 mg/kg or 5 mg/kg) and no significant rotational asymmetry. In conclusion, the present results indicate that glutamatergic corticostriatal afferents are essential for the contraversive rotational behavior but not the striatal hyperexpression of Fos observed in response to amphetamine early after 6-OHDA lesion, and suggest that intense dopaminergic stimulation of striatal neurons is sufficient for induction of Fos, but that concurrent glutamatergic stimulation is necessary for the motor response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050389
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    Facilitation of learning after lesions of the tuberomammillary nucleus region in adult and aged rats (1998)
    Springer
    Experimental brain research 118 (1998), S. 447-456 
    Details
    ISSN: 1432-1106
    Keywords: Key words Posterior hypothalamus ; Histamine ; Memory ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The tuberomammillary nucleus (TM) located in the posterior part of the hypothalamus is the main source of neuronal histamine in the central nervous system. Recent work from our laboratories has indicated an involvement of the TM region in neuronal plasticity and reinforcement processes. In the present study, we investigated the effects of TM lesions on the performance of adult and aged Wistar rats in a set of learning tasks, which differed in terms of complexity and reward contingencies (habituation learning, inhibitory avoidance, discrimination learning, Morris water maze). An improvement was found in every test applied, indicating that TM lesions seem to generally enhance learning and memory capacities independent of the special demands of a given task. Age-related learning deficits were strongly diminished. Immunohistochemistry revealed that the excitotoxic lesions used to destroy the TM region led to a marked decrease in the number of histamine-positive neurons in the vicinity of the injection site, indicating an involvement of the brain histaminergic system in the observed behavioral changes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050301
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  • 45
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    Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter II. Evidence from selective inactivation of cell bodies and axon initial segments (1998)
    Springer
    Experimental brain research 118 (1998), S. 489-500 
    Details
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Brain slice ; Intracortical microstimulation ; NMDA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The results presented in the companion paper showed that extracellular electrical stimulation of the gray matter directly activates axons, but not cell bodies. The second set of experiments presented here was designed to separate the contribution of the axon initial segments and cell bodies from that of the axonal branches to the pool of presynaptic neuronal elements activated by electrical stimulation. For that purpose, N-methyl-d-aspartate (NMDA) iontophoresis was used to induce a selective inactivation of the cell body and of the adjoining portion of the axon by depolarization block, without affecting axonal branches that lack NMDA receptors. After NMDA iontophoresis, the neurons located near the iontophoresis electrode became unable to generate action potentials in an irreversible manner. When the NMDA-induced depolarization block was performed at the site of electrical stimulation, an unexpected increase in the amplitude of the orthodromic responses was observed. Several control experiments suggested that the field potential increase was due to changes of the local environment in the vicinity of the iontophoresis pipette, which led to an increased excitability of the axons. After the period of superexcitability, the orthodromic responses displayed an amplitude that was 15—20% lower than that observed before the NMDA-induced depolarization block, even though cell bodies and axon initial segment at the site of stimulation could not be activated by electrical stimulation. This result shows a low contribution for axon initial segments to the pool of neuronal elements activated by the electrical stimulation. Altogether, these experiments demonstrate that the postsynaptic responses obtained after electrical stimulation of the cortical gray matter result almost exclusively from the activation of axonal branches. Since the neocortex is organised as a network of local and long-range reciprocal connections, great attention must be paid to the interpretation of data obtained with electrical stimualtion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050305
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  • 46
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    Facilitatory effects of thalamic reticular nucleus lesions on two-way active avoidance in rats (1998)
    Springer
    Experimental brain research 118 (1998), S. 511-516 
    Details
    ISSN: 1432-1106
    Keywords: Key words Thalamic reticular nucleus ; Learning ; Memory ; Two-way active avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two experiments were performed in order to study the effects of lesions of the rostral thalamic reticular nucleus (Rt) on two-way active avoidance. Male wistar rats were subjected to either a bilateral electrolytical lesion of the rostral Rt or to control procedures. After recovery, all rats were trained in either a distributed (five training sessions, ten trials each; experiment I) or a massed (a single 30-trials session; experiment II) two-way, active-avoidance task. The level of long-term retention of the task was assessed 10 days later. Lesioned rats showed an overall higher performance than control rats both in experiment I (with lesions affecting the rostral Rt and small portions of some adjacent nuclei) and in experiment II (with lesions almost restricted to the rostral Rt). In contrast, detrimental effects on other tasks have been reported in the literature. Although it cannot be ruled out that those differences might be due to methodological factors, they also might be indicative of an action of rostral Rt lesions on certain mechanisms (either indirectly or directly related to information processing) that could be differentially required depending on the kind of learning task. The latter possibility is discussed in terms of the role played by this nucleus as a modulator of thalamocortical transmission, attentional mechanisms and cortical arousal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050307
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    Comparison of the rat dorsal and ventral striatopallidal system A study using the GABAA-receptor α1-subunit and parvalbumin immunolabeling (1998)
    Springer
    Experimental brain research 121 (1998), S. 215-221 
    Details
    ISSN: 1432-1106
    Keywords: Key words GABAA-receptor α1-subunit ; Parvalbumin ; Striatum ; Pallidum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The ventral striatum is more closely related to limbic brain regions than the dorsal striatum in spite of the remarkable similarities in the structural organization between these two brain regions. The present study is focused on the comparison of ventral striatopallidal territories and the dorsal striatopallidal system regarding the GABAA-receptor α1-subunit and parvalbumin immunoreactivity, as these markers showed specific distribution patterns and coexpression sites in the more intensely studied dorsal regions. Our investigations revealed that: (1) Parvalbumin single-labeled cells and a moderate number of neurons single-labeled with the GABAA-receptor α1-subunit exist not only in the dorsal but also in the ventral striatum, including the striatal cell bridges. In addition, morphologically similar neurons positive for the α1-subunit were also found in the corpus callosum and anterior commissure. (2) A small number of double-labeled neurons was seen not only in dorsal but also in ventral striatal regions. Such cells were mainly located near the border with the globus pallidus and ventral pallidum. They are likely to represent a further type of striatal neuron. (3) The vast majority of neurons in the entopeduncular nucleus, the homologue of the primate internal globus pallidus segment, coexpressed α1-subunit and parvalbumin immunoreactivity, as reported previously for the other pallidal compartments. (4) The islands of Calleja adjoining the ventral pallidal extensions in the olfactory tubercle exhibited a strong α1-subunit immunoreactivity in the neuropil as well as somata single- or double-labeled for both markers. Our findings indicate that the dorsal and ventral striatopallidal compartments are similarly organized in general with respect to the occurrence and distribution of single- and double-labeled parvalbumin-immunoreactive and GABAA-receptor α1-subunit-immunoreactive neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050454
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    Bötzinger-complex expiratory neurons monosynaptically inhibit phrenic motoneurons in the decerebrate rat (1998)
    Springer
    Experimental brain research 122 (1998), S. 149-156 
    Details
    ISSN: 1432-1106
    Keywords: Key words Respiration ; Bötzinger complex ; Phrenic motoneurons ; Bulbospinal expiratory neurons ; Intracellular recording ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We examined respiratory neurons in the Bötzinger complex of the medulla oblongata in 18 vagotomized, paralyzed, ventilated, and decerebrated rats and tested the hypothesis that bulbospinal expiratory neurons in this region monosynaptically inhibit phrenic motoneurons. First, we surveyed the types of respiratory neurons found in the Bötzinger complex; only 11 of the 98 (∼11%) examined were bulbospinal, and all discharged only during late expiration (E2), usually with an augmenting discharge frequency (AUG). Then, we examined the spinal projections of 34 E2-AUG neurons using antidromic activation and found that all projected as far as the C4 or C5 segments of the spinal cord but no further caudally. Most (30, ∼88%) had only unilateral projections, the majority (25, ∼83%) ipsilateral, but 4 neurons (∼12%) had bilateral projections. Their axons could be antidromically activated at low currents (less than 10 μA) in the dorsal-lateral part of the spinal cord at the C2–3 border; 0.5–1.2 mm (mean±SD 0.84±0.23 mm) below the dorsal surface and 0.7–1.5 mm (1.19±0.25 mm) lateral from the midline. We sought evidence for connections from bulbospinal E2-AUG neurons to 118 phrenic motoneurons by computing spike-triggered averages (STAs) of their intracellular potentials triggered by the action potentials of 38 unilaterally-projecting E2-AUG neurons. Resting phrenic motoneuron membrane potentials ranged from –40 to –75 mV (–56±8 mV) and fluctuations with the respiratory cycle from 7 to 20 mV (14±4 mV). Of the 118 STAs computed, hyperpolarizations were evident in 18 (∼15%) STAs, evoked by 11 of 38 (∼29%) E2-AUG neurons. Their amplitudes varied from 35 to 550 μV (105±113 μV), 10–90% fall times from 0.4 to 0.9 ms (0.63±0.17 ms), and half-amplitude widths from 1.3 to 3.2 ms (2.0±0.52 ms). Most (16/95, ∼17%) of the STAs that displayed hyperpolarizations were associated with ipsilateral trigger neurons but some (2/23, ∼9%) resulted from contralateral trigger neurons. We conclude that Bötzinger-complex, expiratory neurons project to the C4 and/or C5 segments of the cervical spinal cord but no further caudal. Their axons are located dorsolaterally in the upper cervical segments of the spinal cord, and they monosynaptically inhibit phrenic motoneurons during the late part of expiration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050502
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    Cyclophosphamide cystitis as a model of visceral pain in rats: a c-fos and Krox-24 study at telencephalic levels, with a note on pituitary adenylate cyclase activating polypeptide (PACAP) (1998)
    Springer
    Experimental brain research 122 (1998), S. 165-174 
    Details
    ISSN: 1432-1106
    Keywords: Key words Urinary bladder ; Inflammation ; Nucleus centralis of amygdala ; Bed nucleus of the stria terminalis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This article is the fifth of a series aimed at mapping brain activities as they result from the development of cyclophosphamide (CP) cystitis in behaving rats using c-fos and Krox-24 expression. The inactive hepatic metabolites of CP are metabolized in the kidney to produce acrolein, which generates cystitis. Data come from animals which were injected once i.p. with either 1 ml saline (sham) or 100 mg/kg CP in 1 ml saline under transient volatile anesthesia and which behaved freely for 1–4 h postinjection, 4 h being the minimum time for cystitis to completely develop. Survival times longer than 4 h were not studied owing to ethical considerations. The first 2 h postinjection cover a period of time over which inputs of multifactorial origin (stress and pain due to the intraperitoneal injection process, possible effects due to the presence of hepatic CP metabolites in blood, cystitis onset) interact in an indistinguishable way; the last 2 h are more cystitis specific as the other effects have vanished. Complete screening of telencephalic levels has been performed. These data complete previously published data at both spinal and subtelencephalic levels. Of all the telencephalic structures, only the bed nucleus of the stria terminalis in the dorsal part of its lateral division (BSTLd) and, to a lesser degree, the nucleus centralis of the amygdala, mostly in its caudal portion (cCeA), appeared to be significantly driven over the most specific cystitis period. Both of these structures had related, but not identical patterns of expression. They both reacted shortly after CP injection, but, while cCeA maintained its activity throughout cystitis development, BSTLd showed a rebound, reaching a peak value when cystitis was fully developed. Both of these areas are the only telencephalic areas to contain high PACAP38 immunoreactivity. This is evidence that, (1) both the BSTLd and cCeA could be the most rostral areas that visceronociceptive inflow would reach when cystitis genesis is under way, and (2) PACAP38 could be one of the neurochemical agents involved in telencephalic visceronociceptive processing. From our complete mapping of brain activities under a fully developed cystitis situation (4 h postinjection), it appears that the activities in BSTLd and cCeA are concomittant with those of both the dorsal vagal complex (DVC), paratrigeminal nucleus (PaT), and the ventrocaudal bulbar reticular formation (vcBRF) at brainstem levels, suggesting they all form the main part of the neural network that subserves the central processing of cystitis-related inputs, comprising pain and associated pseudoaffective responses. Both the DVC and BSTLd, which are the most powerfully driven areas, would be particularly important in such a way. The origin of these activities should be found in both vagal (as sensed through PaT activity) and spinal (pelvic) influences. This network profoundly differs from those reported for painful situations, either somatic or visceral, which controversally accompany positive cardiac inotropism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050504
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  • 50
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    Hypothermia attenuates hyperglycolysis in the periphery of ischemic core in rat brain (1998)
    Springer
    Experimental brain research 122 (1998), S. 333-338 
    Details
    ISSN: 1432-1106
    Keywords: Key words Hypothermia ; Cerebral ischemia ; Glucose metabolism ; Middle cerebral artery occlusion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Hypothermia has proven to be neuroprotective against ischemic brain injury. However, the exact mechanism has not yet been fully understood. In this study, we investigated the effects of hypothermia on cerebral glucose metabolism and blood flow in focal ischemic rats. Rats were divided into normothermic (37±0.5°C) and hypothermic (30±0.5°C) groups. Focal cerebral ischemia was induced by middle cerebral and ipsilateral common carotid arteries occlusion. Two hours after ischemia, autoradiographic studies of 2-deoxyglucose and iodoantipyrine were performed to measure local cerebral glucose utilization (LCGU) and cerebral blood flow. LCGU in the ischemic core was excessively reduced in both groups. However, a marked increase in LCGU was observed in the boundary zone of the ischemic core in normothermic rats. On the other hand, hyperglycolysis in the boundary zone of the ischemic core was suppressed in hypothermia. This attenuation of hyperglycolysis might be closely related to survival of the ischemic penumbra in hypothermia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050521
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    Anxiolytic-like behavior after lesion of the tuberomammillary nucleus E2-region (1998)
    Springer
    Experimental brain research 119 (1998), S. 260-264 
    Details
    ISSN: 1432-1106
    Keywords: Key words Tuberomammillary nucleus ; Ibotenic acid ; Fear and Anxiety ; Elevated plus-maze ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The tuberomammillary nucleus (TM), located in the posterior hypothalamic region, consists of five subgroups and is the only known source of brain histamine. In the present experiment, rats received bilateral ibotenic acid or sham lesions in the rostroventral part of the TM (E2-region). Three weeks later they were tested on the elevated plus-maze test of fear and anxiety. Lesions in the tuberomammillary E2-region elevated the time spent on the open arms, as well as excursions into the end of the open arms, increased scanning over the edge of an open arm, and decreased risk-assessment from an enclosed arm. Thus, partial destruction of TM intrinsic neurons can induce anxiolytic-like effects which are possibly related to a lesion-induced reduction of histaminergic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050340
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    Intranigral ventral mesencephalic grafts and nigrostriatal injections of glial cell line-derived neurotrophic factor restore dopamine release in the striatum of 6-hydroxydopamine-lesioned rats (1998)
    Springer
    Experimental brain research 119 (1998), S. 287-296 
    Details
    ISSN: 1432-1106
    Keywords: Key words Glial cell line-derived neurotrophic factor ; Dopamine ; Parkinson’s disease ; Substantia nigra grafts ; Voltammetry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously reported that grafting of fetal ventral mesencephalic (VM) tissue to the nigral region of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats, in conjunction with glial cell line-derived neurotrophic factor (GDNF) injection between nigra and striatum, restores nigrostriatal tyrosine hydroxylase (TH) immunoreactivity. In this study, we investigated the electrochemical indices of dopamine (DA) release in these grafted animals in the striatum and nigra. Adult Sprague-Dawley rats were anesthetized and unilaterally injected with 6-OHDA into the medial forebrain bundle. The completeness of lesions was tested by measuring methamphetamine-induced rotations. One to two months after 6-OHDA administration, fetal VM tissues were grafted in the lesioned nigral area followed by injection of GDNF, brain-derived neurotrophic factor (BDNF), or phosphate-buffered saline (PBS), along a tract from nigra to striatum. Animals receiving transplantation and GDNF, but not BDNF or PBS, injection showed a significant decrease in rotation 1–3 months after grafting. High-speed chronoamperometric recording techniques, using Nafion-coated carbon fiber electrodes, were used to evaluate DA overflow in the striatum. We found that 6-OHDA lesions resulted in a loss of KCl-induced DA overflow in the urethane-anesthetized rats. Three months after GDNF-bridged grafting, application of KCl elicited DA release both in nigra and striatum. The KCl-evoked DA release area was limited to the GDNF-bridging tract in the striatum. On the other hand, KCl did not induce DA release in the BDNF- or PBS-bridged grafts. Immunocytochemical studies indicated that TH-positive neurons and fibers were found in the nigra and striatum after GDNF-bridged grafting. Taken together, our data suggest that fetal nigral transplantation and GDNF injection may restore the nigrostriatal DA pathway and DA release in these hemiparkinsonian animals and support the hypothesis of trophic activity of GDNF on fiber outgrowth from midbrain DA neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050344
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    Comparison of mesencephalic free-floating tissue culture grafts and cell suspension grafts in the 6-hydroxydopamine-lesioned rat (1998)
    Springer
    Experimental brain research 119 (1998), S. 345-355 
    Details
    ISSN: 1432-1106
    Keywords: Key words Neural transplantation ; Tyrosine hydroxylase ; Calcium-binding proteins ; Parkinson’s disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Ventral mesencephalon (VM) of fetal rat and human origin grown as free-floating roller-tube (FFRT) cultures can survive subsequent grafting to the adult rat striatum. To further explore the functional efficacy of such grafts, embryonic day 13 ventral mesencephalic tissue was grafted either after 7 days in culture or directly as dissociated cell suspensions, and compared with regard to neuronal survival and ability to normalize rotational behavior in adult rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. Other lesioned rats received injections of cell-free medium and served as controls. The amphetamine-induced rotational behavior of all 6-OHDA-lesioned animals was monitored at various time points from 18 days before transplantation and up to 80 days after transplantation. Tyrosine hydroxylase (TH) immunostaining of the histologically processed brains served to assess the long-term survival of grafted dopaminergic neurons and to correlate that with the behavioral effects. Additional cultures and acutely prepared explants were also fixed and stored for histological investigation in order to estimate the loss of dopaminergic neurons in culture and after transplantation. Similar behavioral improvements in terms of significant reductions in amphetamine-induced rotations were observed in rats grafted with FFRT cultures (127%) and rats grafted with cell suspensions (122%), while control animals showed no normalization of rotational behavior. At 84 days after transplantation, there were similar numbers of TH-immunoreactive (TH-ir) neurons in grafts of cultured tissue (775 ± 98, mean ± SEM) and grafts of fresh, dissociated cell suspension (806 ± 105, mean ± SEM). Cell counts in fresh explants, 7-day-old cultures, and grafted cultures revealed a 68.2% loss of TH-ir cells 7 days after explantation, with an additional 23.1% loss after grafting, leaving 8.7% of the original number of TH-ir cells in the intracerebral grafts. This is to be compared with a survival rate of 9.1% for the TH-ir cells in the cell-suspension grafts. Immunostaining for the calcium-binding proteins calretinin, calbindin, and parvalbumin showed no differences in the neuronal expression of these proteins between the two graft types. In conclusion, we found comparable dopaminergic cell survival and functional effects of tissue-culture grafts and cell-suspension grafts, which currently is the type of graft most commonly used for experimental and clinical grafting. In this sense the result is promising for the development of an effective in vitro storage of fetal nigral tissue, which at the same time would allow neuroprotective and neurotrophic treatment prior to intracerebral transplantation.
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    URL: http://dx.doi.org/10.1007/s002210050350
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    Correlation of electrophysiology, morphology, and functions in corticotectal and corticopretectal projection neurons in rat visual cortex (1998)
    Springer
    Experimental brain research 119 (1998), S. 375-390 
    Details
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Superior colliculus ; Nucleus of the optic tract ; Electrophysiology ; Morphology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In most mammals the superior colliculus (SC) and the pretectal nucleus of the optic tract (NOT) receive direct input from the ipsilateral visual cortex via projection neurons from infragranular layer V. We examined whether these projection neurons belong to different populations and, if so, whether it is possible to correlate the electrophysiological features with the suggested function of these neurons. Projection cells were retrogradely labeled in vivo by rhodamine-coupled latex beads or fast blue injections into the SC or the NOT 2–5 days prior to the electrophysiological experiment. Intracellular recordings of prelabeled neurons were made from standard slice preparations and cells were filled with biocytin in order to reveal their morphology. Both cell populations consist of layer V pyramids with long apical dendrites that form terminal tufts in layer I. In electrophysiological terms, 12 of the corticotectal cells could be classified as intrinsically bursting (IB), while two neurons showed a doublet firing characteristic and one neuron was classified as regular-spiking (RS). Intracortical microstimulation of cortical layer II/III revealed that SC-projecting neurons responded optimally to stimulation sites up to a distance of 1000 μm from the recorded cell. The morphological features of the SC-projecting cells reveal an apical dendritic tuft in layer I with a lateral extension of 300 μm, a mean spine density of 65 spines per 40 μm on the apical dendrites located in layer II/III, and a bouton density of 13 boutons per 100 μm on the intracortical axons. Sixteen NOT-projecting neurons exhibited an IB and five cells an RS characteristic. Intracortical microstimulation of cortical layer II/III showed that NOT-projecting neurons responded optimally to stimulation sites up to a distance of 1500 μm. Their morphological features consist of an apical dendritic tuft with a lateral extension of 500 μm, a mean spine density of 25 spines per 40 μm on the apical dendrites located in layer II/III, and a bouton density of 6 boutons per 100 μm on the intracortical axons. When the passive membrane parameters, responses to intracortical microstimulation in layer V, the extension of the basal dendritic field, and spine densities in layers I or V were compared between SC- and NOT-projecting cells, no differences were revealed. Differences were only consistently found in the supragranular layers, either for morphological parameters or for intracortical microstimulation. The results suggest that NOT-projecting and SC-projecting neurons, although biophysically similar, could integrate and transmit different spatial aspects of cortical visual information to their target structures.
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    URL: http://dx.doi.org/10.1007/s002210050353
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    The effects of cytotoxic entorhinal lesions and electrolytic medial septal lesions on the acquisition and retention of a spatial working memory task (1998)
    Springer
    Experimental brain research 119 (1998), S. 517-528 
    Details
    ISSN: 1432-1106
    Keywords: Key words Entorhinal cortex ; Medial septal nucleus ; Working memory ; T-maze ; Delayed matching-to-position ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rats with lesions either of medial septal nucleus (MSN) or the entorhinal cortex (ECx) were compared postoperatively with unoperated controls in a discrete-trial, delayed matching-to-position (DMTP) task, conducted on an elevated T-maze. A DMTP trial consisted of two consecutive visits to the maze: an information run and a choice run. The animals were first forced to visit a randomly selected choice arm in the information run. In the choice run, the correct response was to match the choice arm that had been visited on the information run, regardless of whether the information run itself had been rewarded or not. MSN animals failed to succeed in this task, performing at close to chance level throughout training. On the other hand, ECx rats consistently perform at a level comparable with that of unoperated controls; both groups attained more than 90% correct after 192 trials. Long-term retention testing was carried out after an intermission of 4 weeks, when the same task was re-administered to the ECx and unoperated control animals. ECx animals showed significantly less saving than controls in the retention test. In contrast, when the retention interval within a DMTP trial was increased by the imposition of a 20-s delay between the information and choice runs, the ECx group was not selectively affected by this manipulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050368
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  • 56
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    Time course of changes in EMG activity of fast muscles after partial denervation (1998)
    Springer
    Experimental brain research 120 (1998), S. 193-201 
    Details
    ISSN: 1432-1106
    Keywords: Key words EMG ; Motor unit activity ; Partial denervation ; Interlimb coordination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  After partial denervation, the remaining motor units (MUs) of adult fast extensor digitorum longus muscle (EDL) expand their peripheral field. The time course of this event was studied using tension measurement and recordings of electromyographic (EMG) activity. The results show that after section of the L4 spinal nerve, when only 5.3 ± 0.63 of the 40 MUs normally supplying EDL muscle remain, the force of individual motor units starts to increase between the 1st and 2nd week after the operation and continues to do so for a further week. The drastic reduction of the number of motoneurones supplying the fast EDL leads to an increase in activity of the remaining MUs. In the 1st week after partial denervation, there was a sharp increase in the EMG activity of remaining motor units. During the next 12 days, this increase became less marked, but EMG activity remained nevertheless significantly higher than that of the unoperated EDL muscle. Many MUs became tonically active during posture. The EMG activity pattern during locomotion was also altered, so that the burst duration was positively correlated with the step cycle duration. Moreover, shortly after partial denervation, the interlimb coordination was disturbed but returned to its original symmetrical use 1–2 weeks later.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050393
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    Developmental changes in NMDA receptor-mediated visual activity in the rat superior colliculus, and the effect of dark rearing (1998)
    Springer
    Experimental brain research 120 (1998), S. 335-344 
    Details
    ISSN: 1432-1106
    Keywords: Key words Plasticity ; Glutamate ; AP5 ; Visual Deprivation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  N-methyl-D-aspartate (NMDA) receptor-mediated activity is considered important for experience-dependent plasticity in the developing visual system. We investigated the influence of age and experience on the role of NMDA receptors in the visual transmission in the superficial grey layer of the superior colliculus (SGS) of the superior colliculus, where, in the adult, NMDA receptors mediate a substantial part of the visual response. In normally reared (postnatal day 14, P14, to adult) rats, visual responses were challenged with NMDA receptor-selective iontophoretic applications of the antagonist D-2-amino-5-phosphonovalerate (AP5). After eye opening (at P14), there was a significant increase in the number of neurones whose visual responses were reduced during AP5 ejection, which peaked at P22 (85%; n = 21), and then declined to adult levels (66%; n = 47) at P25. The mean reduction of the response (from control levels) by AP5 was similar at all ages (approximately 40%). Dark rearing had striking effects on the role of NMDA receptors in visual transmission, especially when comparisons were made between age-matched subjects greater than P25. In these subjects, AP5 ejection reduced the visual responses of all neurones studied. In addition, AP5 ejection caused a significantly larger reduction of visual responses in dark-reared rats (mean reduction 62 ± 4; n = 29) compared with age-matched controls (mean reduction 44 ± 8; n = 23). The D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the visual responses of every neurone studied and there were no age- or experience-dependent effects. We conclude that NMDA receptors, but not AMPA receptors, assume greater importance for visual transmission in the SGS of dark-reared rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050407
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    Dual (excitatory and inhibitory) calretinin innervation of AMPA receptor-containing neurons in the rat lateral septum (1998)
    Springer
    Experimental brain research 119 (1998), S. 65-72 
    Details
    ISSN: 1432-1106
    Keywords: Key words Glutamate receptor ; GABA ; Double immunostaining ; Colocalization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A recent study demonstrated both an extrinsic and an intrinsic calretinin (CR) innervation of the rat septal complex and that a population of the extrinsic calretinin fibers is aspartate/glutamate-containing. The aim of this study was to determine which types (GluR1, GluR2/3, or both) of AMPA receptor-containing lateral septal area neurons are innervated by extrinsic and intrinsic CR neurons and whether the intrinsic CR cells are GABAergic. Light- and electron-microscopic single immunostaining for CR, GluR1, and GluR2/3, as well as light- and electron-microscopic-double immunostaining experiments for CR plus GluR1 and CR plus GluR2/3 were performed in the lateral septal area. Furthermore, the ″mirror″ colocalization technique was employed on consecutive vibratome sections of the septal complex to investigate whether the intrinsic septal CR neurons are GABAergic. The results are summarized as follows: (1) both GluR1- and GluR2/3-immunoreactive neurons are innervated by CR-containing fibers; (2) the majority of these synapses, observed mainly on the soma and, to a lesser extent, on proximal dendrites of AMPA receptor-containing neurons, represent asymmetric synaptic membrane specializations; (3) a minority of CR-containing axon terminals associated with both GluR1- and GluR2/3-immunoreactive neurons form symmetric contacts, predominantly on their soma; and (4) 93% of the lateral septal area CR cells are GABAergic. These observations indicate that both GluR1- and GluR2/3-containing lateral septal area neurons receive a dual intrinsic and extrinsic CR innervation. The former (intrinsic) CR boutons are GABAergic, while the latter form asymmetric synaptic contacts, are excitatory, and probably originate in the supramammillary area, since previous work has demonstrated that a population of supramammillo-septal fibers contain aspartate and/or glutamate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050320
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    Electronic Resource
    Acute and long-lasting changes in extracellular-matrix chondroitin-sulphate proteoglycans induced by injection of chondroitinase ABC in the adult rat brain (1998)
    Springer
    Experimental brain research 121 (1998), S. 300-310 
    Details
    ISSN: 1432-1106
    Keywords: Key words Extracellular matrix ; Proteoglycans ; Chondroitinase ; Cerebral cortex ; Plasticity ; Regeneration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Lattice-like perineuronal accumulations of extracellular-matrix proteoglycans have been shown to develop during postnatal maturation and to persist throughout life as perineuronal nets (PNs) in many brain regions. However, the dynamics of their reorganization in adults are as yet unknown. The aim of the present study was to examine the capability of PNs for reconstitution after experimental destruction and to search for possible consequences of extracellular-matrix degradation for neurons and glial cells. The changes were induced by single intracortical injections of Proteus vulgaris chondroitinase ABC and studied after postinjection periods of 1 day to 5 months. The N-acetylgalactosamine-binding Wisteria floribunda agglutinin (WFA), an antibody against chondroitin-sulphate proteoglycans, three antibodies recognizing initial chondroitin or chondroitin-sulphate moieties (’stubs’) of proteoglycan core proteins, an antibody against the hyaluronan-binding protein component of versican, and biotinylated hyaluronectin, which binds to hyaluronan, were used as cytochemical markers. One day postinjection, the WFA-binding sites and hyaluronan were shown to be almost completely removed within a circumscribed digestion zone. The staining of different core-protein components revealed only fragments of PNs. These changes were found to be partly compensated 4 weeks after injection of chondroitinase ABC. After 8 and 12 weeks postinjection, the cytochemical and structural characteristics as well as the area-specific distribution patterns of PNs were progressively reconstituted. At 5 months postinjection, they could not be distinguished from those in untreated tissue. In contrast to such transient changes, a diffuse chondroitin-sulphate proteoglycan immunoreactivity persisted in the neuropil. Loss of neurons or alterations of their structure as well as reactions of glial cells were not observed. We conclude from this study that PNs, enzymatically destroyed in the adult rat brain, can be completely reconstituted, but the restoration of their extracellular-matrix components needs several months.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050463
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    Electronic Resource
    Reaction of Müller cells after increased intraocular pressure in the rat retina (1998)
    Springer
    Experimental brain research 121 (1998), S. 419-424 
    Details
    ISSN: 1432-1106
    Keywords: Key words Glial fibrillary acidic protein ; Müller cell ; Increased intraocular pressure ; Retina ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Using light microscopy and immunocytochemistry, we investigated the morphological changes of retinal tissues and the reaction of Müller cells in the ischemic rat retina induced by increasing intraocular pressure. At early stages (from 1 h to 24 h after reperfusion), cells in the ganglion cell layer and in the inner nuclear layer showed some degenerative changes, but at later stages (from 72 h to 4 weeks) marked degenerative changes occurred in the outer nuclear layer (ONL). At 4 weeks after reperfusion, the ONL was reduced to 1 or 2 cell layers. Immunoreactivity for glial fibrillary acidic protein (GFAP) appeared in the endfeet and distal processes of Müller cells as of 1 h after reperfusion. GFAP immunoreactivity in Müller cells increased up to 2 weeks and then decreased at 4 weeks after reperfusion. Our findings suggest that Müller cells are involved in the pathophysiology of retinal ischemia through the expression of GFAP. The degree of GFAP expression in Müller cells closely correlated with that of the degeneration of retinal neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050476
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    Renal excretory responses of taurine-depleted rats to hypotonic and hypertonic saline infusion (1998)
    Springer
    Amino acids 15 (1998), S. 109-116 
    Details
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Rat ; Natriuresis ; Hypotonic saline ; Hypertonic saline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male Wistar-Kyoto rats were given either tap water (control) or 3%β-alanine (taurine-depleted) for three weeks. To prepare for the kidney function studies, the animals were then implanted with femoral vessels and bladder catheters. Two days after surgery, each rat was given an intravenous infusion of saline at the rate of 50μl/min and urine samples were collected at specific time intervals. An isotonic saline solution (0.9% NaCl) was infused for determination of baseline parameters and was followed by the infusion of a hypotonic saline solution (0.45% NaCl). Two days later, the infusion protocol was repeated in the same animals; however, a hypertonic saline solution (1.8% NaCl) was substituted for the hypotonic saline solution. Renal excretion of fluid and sodium increased in the control, but not taurine-depleted, rats during the hypotonic saline infusion. Interestingly, diuretic and natriuretic responses were similar between the groups during hypertonic saline infusion. The results suggest that taurine-depletion in rats affects renal excretory responses to a hypotonic, but not a hypertonic, saline solution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01345284
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    Electronic Resource
    Expression and localization of cysteine dioxygenase mRNA in the liver, lung, and kidney of the rat (1998)
    Springer
    Amino acids 15 (1998), S. 143-150 
    Details
    ISSN: 1438-2199
    Keywords: Amino acids ; In situ hybridization ; Cysteine dioxygenase ; Liver ; Lung ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expressions of cysteine dioxygenase (CDO) gene in the liver, lung, skeletal muscle, and kidney were studied byin situ hybridization with a cDNA probe from rat liver CDO under normal conditions. Significant expression of the CDO gene was detected in the liver, lung, and kidney, but not skeletal muscle. In the liver, the signal was confined to the cytoplasm of the hepatocytes. Furthermore, the signal was stronger in the periportal than that in the perivenous areas. In the lung, an intensive signal was found in the bronchiolar epithelium. As to the kidney, an intensive signal was observed in the distal convoluted tubules, while no signal was found in the proximal convultions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01345287
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    Electronic Resource
    Whole body autoradiographic study on the distribution of14C-d-serine administered intravenously to rats (1998)
    Springer
    Amino acids 15 (1998), S. 351-361 
    Details
    ISSN: 1438-2199
    Keywords: Amino acids ; 14C-l-Serine ; Rat ; Whole body autoradiography ; Accumulation ; Kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of radioactivities in rats following intravenous administration of14C-d- or -l-serine was investigated by whole body autoradiography. The radioactivities were distributed throughout the whole body in both cases with the greatest amount being found in the pancreas. D- andl- Serine levels in the pancreas were determined by high-performance liquid chromatography with a chiral column which revealed, for the first time, the existence ofd-serine in the rat pancreas (12.6 ± 7.90 nmol/g wet tissue) together with a much higher concentration (924 ± 116 nmol/g) ofl-serine. The results suggested that exogenous D-serine of dietary origin contributed at least in part to the D-serine levels found in mammalian tissues. The accumulation of radioactivity in the kidney, especially in the corticomedullary area, even at 24 hr after administration of14C-l-serine suggested a possible link between acute necrosis of the renal proximal tubules and the administration of a large dose of D-serine [Am J Pathol 77: 269–282 (1974)].
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01320899
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    Release of endogenous excitatory amino acids in the neostriatum of the rat under physiological and pharmacologically-induced conditions (1998)
    Springer
    Amino acids 14 (1998), S. 197-203 
    Details
    ISSN: 1438-2199
    Keywords: Basal ganglia ; Excitatory amino acids ; Monoamines ; Neuropeptides ; Microdialysis ; Immunocytochemistry ; Parkinson's disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary There is immunohistochemical evidence suggesting that glutamate (Glu) is released from nerve terminals and acts, via several receptor subtypes, as a major excitatory neurotransmitter in the cortico-striatal pathway of the rat. Aspartate (Asp) is also present in cortico-striatal neurons, but its role as a neurotransmitter has been questioned, since, in contrast to Glu, it has not been demonstrated in presynaptic vesicles. Glu and Asp can be found at subμM concentrations in the extracellular compartment of most areas of the basal ganglia. Their concentrations are largely regulated by transport mechanisms, but also by a synaptotagmin-dependent exocytotic release, and are sufficiently high to occupy junctional and extrajunctional receptors. We have investigated whether Glu and Asp release in the neostriatum can be selectively modulated by different neuronal systems. Dopamine (DA) and cholecystokinin (CCK) selectively stimulate Asp release, via D1 and CCKB receptor subtypes, respectively. Also opioid κ-agonists increase Asp release. We propose that the selective modulation of Asp release by D1−, CCKB- and κ agonists involves striatal neurons containing Asp, but not Glu. In contrast, local perfusion with the ,μ-opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-ThrPen-Thr-NH2 (CTOP) increases both Glu and Asp release. This effect is probably exerted on cortico-striatal terminals, via presynaptic inhibitory μ-receptors. Thus, these results demonstrate that extracellular levels of Glu and Asp are modulated differentially by different neuronal systems, and suggest that in the neostriatum of the rat there are neuronal populations using Glu and/or Asp as messenger(s).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01345262
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    Fetal adrenal transplants respond to ACTH and prevent addisonian crisis in adrenalectomized rats (1998)
    Springer
    Pediatric surgery international 13 (1998), S. 271-273 
    Details
    ISSN: 1437-9813
    Keywords: Key words Fetal transplantation ; Adrenals ; Addisonian crises ; Rat ; Adrenocorticotropic hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study investigates whether fetal adrenal transplants into the omentum of adrenalectomized rats will be integrated into the recipient's endocrine system to provide competent adrenocortical function. The results demonstrate that fetal adrenals graft with a rich vascular supply, mature histologically, and produce increasing levels of corticosterone. When bilateral adrenalectomy is performed in the recipient, survival is prolonged and addisonian crisis can be prevented. Moreover, adrenocorticotrophic hormone levels decrease with increasing levels of corticosterone, indicating that the fetal grafts are integrated into the physiological pituitary-adrenocortical feedback system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050314
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    Locally infused taurine, GABA and homotaurine alter differently the striatal extracellular concentrations of dopamine and its metabolites in rats (1998)
    Springer
    Amino acids 15 (1998), S. 117-134 
    Details
    ISSN: 1438-2199
    Keywords: Amino acids ; Striatal dopamine release ; Intrastriatal taurine ; GABA ; Homotaurine ; Microdialysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studiedin vivo the effects of locally infused taurine (50, 150, and 450 mM) on the striatal dopamine and its metabolites in comparison with those of GABA and homotaurine, a GABAA receptor agonist, in freely moving rats. The extracellular dopamine concentration was elevated maximally 2.5-, 2- and 4-fold by taurine, GABA and homotaurine, respectively. At 150 mM concentration, at which the maximum effects occurred, homotaurine increased the extracellular dopamine more than taurine or GABA. When taurine and GABA were infused simultaneously with tetrodotoxin the output of dopamine did not differ from that in the presence of tetrodotoxin alone. In comparison, tetrodotoxin did not inhibit the increase in extracellular dopamine caused by homotaurine. Furthermore, omission of calcium from the perfusion fluid inhibited the increase of extracellular dopamine caused by GABA. However, it did not block the increase of dopamine caused by taurine or homotaurine. The present study suggests that the effects of intrastriatal taurine, GABA and homotaurine on the striatal extracellular dopamine differ. Thus, these amino acids seem to affect the striatal dopaminergic neurons via more than one mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01345285
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    The difference of HSP72 induction in rat’s systemic organs after burn injury depends on burned body surface area (1998)
    Springer
    European journal of plastic surgery 21 (1998), S. 91-94 
    Details
    ISSN: 1435-0130
    Keywords: Key words Burn injury ; Stress protein ; Systemic organs ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously reported that in severely burned rats, the induction of 72-kD stress protein (HSP72) increased in various systemic organs. In this present study, in order to compare the stress response of systemic organs to burn injury of a smaller total body surface area with those of an extensive burn, we investigated the induction of 72-kD heat shock protein (HSP72) in various organs (brain, hypophysis, lung, heart, liver, pancreas, spleen, kidney, adrenal gland, and skeletal muscle) of burned rats. A dermal burn was developed on the skin by immersing the rats in hot water (90° C) for three seconds. At 0, 24 and 48 h after burn injury, the HSP72 induction of various organs was examined by Western blot analysis. In the single hind leg burn, the level of HSP72 did not increase at any time in all ten organs. In the double hind leg burn, at 48 h, the induction of HSP72 increased more than 1.5 fold compared to the control in the hypophysis (1.6 fold) and the heart (1.8 fold). These results indicate that the double hind leg burn causes a stress response in the hypophysis and the heart, while the single hind leg burn does not cause this stress response. In extensively burned rats, the degree of the stress response of the systemic organs to the burn injury depends on the burn size, and the intensity of “burn stress” to the systemic organs in a double or single hind leg burn is relatively small compared with those in extensive burns at the molecular level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002380050034
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    Additive effect of concomitant multiple low-dose doxorubicin and thoracic irradiation on ex vivo cardiac performance of the rat heart (1998)
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 148-154 
    Details
    ISSN: 1432-1335
    Keywords: Key words Irradiation ; mld-doxorubicin ; Isolated working rat heart preparation ; Heart function ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of doxorubicin alone or combined with local heart irradiation on ex vivo cardiac performance were studied in Sprague-Dawley rats. Rats were treated with doxorubicin either administered as a single bolus injection or administered weekly during a period of 10 weeks. In “combined” experiments, local heart irradiation with a single dose of 15 Gy was given prior to drug administration. Evaluation of cardiac performance was performed 14 weeks after initiation of treatment. At drug doses that were tolerated by the rat, single injections with doxorubicin (sd-DXR; up to a dose of 5 mg/kg) did not lead to a change in cardiac performance whereas multiple injections with low-dose doxorubicin (mld-DXR; up to a cumulative dose of 20 mg/kg) led to a dose-dependent decrease in cardiac function. Extracardial toxicity as a result of mld-DXR (cumulative dose ≤15 mg/kg) was mild when compared to the toxicities observed after sd-DXR (5.0 and 7.5 mg/kg). When administration of mld-doxorubicin was preceded by 15 Gy, cardiac performance further decreased. The present data indicate that the interaction between doxorubicin and local heart irradiation with a dose of 15 Gy is additive, when the treatments are given concomitantly. Irradiation did not lead to an increase of DXR-mediated extracardial toxicities. The isolated working rat heart preparation offers a reliable method to evaluate the effects of doxorubicin and new anthracycline analogue on the heart.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050148
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    Effects of space flight on GLUT-4 content in rat plantaris muscle (1998)
    Springer
    International journal of biometeorology 41 (1998), S. 101-104 
    Details
    ISSN: 1432-1254
    Keywords: Key words Space flight ; Rat ; Plantaris muscle ; GLUT-4 ; Citrate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract  The effects of 14 days of space flight on the glucose transporter protein (GLUT-4) were studied in the plantaris muscle of growing 9-week-old, male Sprague Dawley rats. The rats were randomly separated into five groups: pre-flight vivarium ground controls (PF-VC) sacrificed approximately 2 h after launch; flight groups sacrificed either approximately 5 h (F-R0) or 9 days (F-R9) after the return from space; and synchronous ground controls (SC-R0 and SC-R9) sacrificed at the same time as the respective flight groups. The flight groups F-R0 and F-R9 were exposed to micro-gravity for 14 days in the Spacelab module located in the cargo bay of the shuttle transport system – 58 of the manned Space Shuttle for the NASA mission named ”Spacelab Life Sciences 2”. Body weight and plantaris weight of SC-R0 and F-R0 were significantly higher than those of PF-VC. Neither body weight nor plantaris muscle weight in either group had changed 9 days after the return from space. As a result, body weight and plantaris muscle weight did not differ between the flight and synchronous control groups at any of the time points investigated. The GLUT-4 content (cpm/µg membrane protein) in the plantaris muscle did not show any significant change in response to 14 days of space flight or 9 days after return. Similarly, citrate synthase activity did not change during the course of the space flight or the recovery period. These results suggest that 14 days of space flight does not affect muscle mass or GLUT-4 content of the fast-twitch plantaris muscle in the rat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004840050060
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  • 70
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    Electronic Resource
    Endosomes: another extra-mitochondrial location of type-1 porin/voltage-dependent anion-selective channels (VDAC) (1998)
    Springer
    Pflügers Archiv 436 (1998), S. 478-480 
    Details
    ISSN: 1432-2013
    Keywords: Key words Chloride channel ; Endosomes ; Porin ; Rat ; Renal cortex ; Voltage-dependent anion channel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Endocytotic vesicles (EV) isolated from rat renal cortex were subjected to SDS-polyacrylamide gel electrophoresis and Western blotting. A monoclonal antibody against human type-1 porin (31 kDa) detected a strong band of 31 kDa. The same antibody has been used as the primary antibody in indirect immunocytochemistry. Light microscopy of cryostat sections of rat renal cortex showed a heavy staining of EV underneath the brush-border membrane. Electron microscopy was performed by ”preembedding immunogold staining” of rat renal cortex, the sections of which showed an extensive labelling of EV with gold particles. These results demonstrate that the expression of type-1 porin is not restricted to outer mitochondrial membranes. The biological function of endosomal type-1 porin has as yet to be ascertained.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050659
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  • 71
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    Luminal ATP induces K+ secretion via a P2Y2 receptor in rat distal colonic mucosa (1998)
    Springer
    Pflügers Archiv 436 (1998), S. 712-716 
    Details
    ISSN: 1432-2013
    Keywords: Key words ATP ; Distal colon ; Exocrine secretion ; K+ secretion ; Luminal receptors ; P2Y2 receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously investigated, in studies of rat distal colonic mucosa, the effect of ATP added to the basolateral side on ion transport and [Ca2+]i. It was demonstrated that ATP acts via a P2Y1 receptor to increase [Ca2+]i and NaCl secretion. In the present study we investigated the effect of luminally added nucleotides (ATP, UTP) on transepithelial voltage (V te) and resistance (R te) in Ussing chamber experiments on rat distal colonic mucosa. Both nucleotides induced a rapid and transient (within 30 s) change of V te to lumen-positive values (resting V te: –2±1 mV; peak V te after 100 µmol/l ATP: +2.4±1.1 mV) and a decrease of R te from 89.9±10.3 to 83.8±9.1 Ωcm2 (n=10). Similar values were obtained with luminal UTP (n=15). The estimated EC50 values for both nucleotides were approximately 6 µmol/l. The ATP-induced V te effect was nearly completely sensitive to Ba2+. Addition of the K+ channel blocker Ba2+ (1 mmol/l) to the luminal solution reversibly inhibited 77±4% (n=5) of the ATP-induced V te effect. Experiments to identify the respective P2 receptor subtype revealed the following rank order of potency at 500 µmol/l agonist: UTP≥ATP〉〉2-methylthio-ATP=ADP〉〉adenosine〉 AMP〉β,γ-methylene-ATP (n=5). This closely resembles the published rank order for the P2Y2 receptor. Using the reverse-transcriptase polymerase chain reaction (RT-PCR) technique P2Y2 receptor-specific mRNA was detected in total RNA extracted from isolated crypts. In summary these data indicate that luminal ATP and UTP act via a P2Y2 receptor in the luminal membrane of colonic mucosa to elicit a transient K+ secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050693
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    The disruption of myofibre structures in rat skeletal muscle after forced lengthening contractions (1998)
    Springer
    Pflügers Archiv 436 (1998), S. 735-741 
    Details
    ISSN: 1432-2013
    Keywords: Key words Actin ; Cytoskeleton ; Desmin ; Dystrophin ; Fibronectin ; Muscle damage ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Specific antibodies against structural proteins (actin, desmin, dystrophin, fibronectin) of muscle fibres were used to study the effect of forced lengthening contractions on muscle microarchitecture. Tibialis anterior (TA) muscle of male Wistar rats were subjected to 240 forced lengthening contractions. At consecutive time points (0, and 6 h, 2, 4, and 7 days) after stimulation, the TA muscle was excised for biochemical and histological assays. β-Glucuronidase activity, a quantitative indicator of muscle damage, showed increased values 2–7 days after the lengthening, peaking on day 4 (11.7-fold increase). A typical course of histopathological changes (myofibre swelling, necrosis and regeneration) was observed. In immunohistochemistry, the earliest abnormality observed was discontinuous dystrophin staining in some swollen fibres immediately after commencement of exercise, while at the same time no alterations occurred in the staining of the other antibodies studied. Six hours later, all the swollen fibres were uniformly desmin as well as dystrophin negative. The great majority, but not all, of the swollen fibres showed disorganized actin staining and intramyocellular localization of fibronectin. The early phase disruption of myofibre structures as measured in this study provides evidence of their central role following damage in skeletal muscle. These results suggest that the sequence of structural changes in the route to muscle fibre necrosis in injury induced by forced lengthening contraction originates in the disruption of the plasma membrane and the intermediate filament, which leads to disturbances in the myofibrillar system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050696
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    Extracellular glutamate increases in rostral ventrolateral medulla during static muscle contraction (1998)
    Springer
    Pflügers Archiv 435 (1998), S. 465-471 
    Details
    ISSN: 1432-2013
    Keywords: Key words Arterial pressure ; Microdialysis ; Excitatory amino acid ; Exercise ; Pressor Reflex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The ventrolateral medulla is an important site involved in increases in arterial pressure and heart rate during static muscle contraction. Glutamate, an excitatory amino acid neurotransmitter, appears to play a role in mediating these responses. We measured glutamate concentration in the extracellular fluid of the rostral ventrolateral medulla during static muscle contraction in anesthetized rats. A 2-min tibial nerve stimulation-evoked muscle contraction increased blood pressure by 30 ± 4 mmHg and heart rate by 32 ± 4 bpm. Extracellular glutamate in the rostral ventrolateral medulla also increased from 9 ± 1 pmol/4 μl to 14 ± 1 pmol/4 μl. Results were repeatable over two subsequent contractions. Tibial nerve stimulation following neuromuscular blockade did not elicit changes in blood pressure, heart rate or extracellular fluid glutamate. Data demonstrate that muscle contraction increases extracellular fluid concentration of glutamate in the rostral ventrolateral medulla, suggesting that rostral ventrolateral medullary glutamate release is a neurochemical change associated with cardiovascular responses during static muscle contraction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050540
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    Expression of sucrase and intestinal-type alkaline phosphatase in colorectal carcinoms in rats treated with methylazoxymethanol acetate (1998)
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 677-682 
    Details
    ISSN: 1432-1335
    Keywords: Key words Small-intestine phenotype ; Sucrase ; Intestinal-type alkaline phosphatase ; Colon cancer ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study the small-intestine phenotype in rat colonic tumors was investigated in terms of sucrase and intestinal-type alkaline phosphatase (I-ALP) activity. F344 rats were given intraperitoneal injections of methylazoxymethanol acetate at a dose level of 25 mg/kg body weight once a week for 8 weeks and were killed 40 weeks after the first injection. Sucrase and I-ALP activities in proximal and distal colon adenocarcinomas were significantly higher than those in the normal colon epithelium. In the jejunum, by contrast, normal tissue had significantly higher levels than tumors. Immunohistochemical staining of I-ALP was also strong in striated cell borders of colon adenocarcinoma cells. These data suggest that, whereas absorptive cells of the small intestine lose their own traits with tumor development, colonocytes acquire phenotypic features of the small intestine. Intestinal enzymes associated with the striated-cell border, such as sucrase and I-ALP, may be useful markers for malignant phenotypic expression in colonocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050231
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    Stimulation of forward locomotion by SCH-23390 and raclopride in d-amphetamine-treated rats (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 593-599 
    Details
    ISSN: 1432-1912
    Keywords: Key words d-amphetamine ; Dopamine receptors ; Locomotor activity ; Raclopride ; SCH-23390 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In d-amphetamine-treated (4.0 mg kg–1 s.c.) rats the selective dopamine D1 and D2/3 receptor antagonists SCH-23390 (2.5–20.0 µg kg–1 s.c.) and raclopride (12.5–100.0 µg kg–1 s.c.), respectively, produced a biphasic pattern of effects on forward locomotion, as observed in an open-field arena (≈0.5 m2). Thus, at the low doses of SCH-23390 (2.5–10.0 µg kg–1) or raclopride (12.5–50.0 µg kg–1), there was a statistically significant increase in forward locomotion, followed by suppression of the behavior at the higher doses. The SCH-23390-induced (5.0 µg kg–1) stimulation of forward locomotion was partially antagonized by concomitant raclopride treatment (12.5–25.0 µg kg–1) and the corresponding raclopride-induced (12.5 µg kg–1) stimulation was fully antagonized by treatment with SCH-23390 (2.5–5.0 µg kg–1). Furthermore, the SCH-23390- or raclopride-induced stimulation of forward locomotion was also antagonized by treatment with the α1-adrenoceptor antagonist prazosin (1.0 mg kg–1 s.c.). These observations suggest that under conditions of an increased general tone at brain dopamine receptors, there is a mutual inhibitory synergy between dopamine D1 and D2/3 receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005213
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    Morphologic and functional consequences of intimal hyperplasia in the rat carotid artery (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 133-142 
    Details
    ISSN: 1432-1912
    Keywords: Key words Intimal hyperplasia ; Potassium chloride ; α1-Adrenoceptor ; Methacholine ; Sodium nitroprusside ; Rat ; Carotid artery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of neointima formation on functional characteristics was investigated in rat carotid artery preparations. The process of intimal hyperplasia development in the injured carotid arteries was followed in time both morphologically and morphometrically. Simultaneously with the loss of endothelial cells due to the balloon injury procedure, the vasodilator responses to methacholine were abolished. The sensitivity for the α1-adrenoceptor agonist phenylephrine appeared to be increased only immediately after injury. The balloon injury method led to significant neointima formation in the rat left common carotid artery 14 days after the intervention. Eight weeks after balloon injury, the neointimal mass reached its maximum. Parallel to the development of intimal hyperplasia, the α1-mediated vasoconstrictor responses to phenylephrine were significantly impaired. After 12 weeks of observation, reoccurrence of mature endothelial cells on the luminal surface of the neointima could be observed. Simultaneously, the vascular responses to phenylephrine and methacholine recovered. The vasoconstrictor responses to high potassium concentrations (100 mM) as well as the vasodilator effects of sodium nitroprusside appeared to be uninfluenced by balloon injury throughout the period of observation. From this study we conclude that both the receptor-mediated contractile responses to α1-adrenoceptor stimulation and the endothelium-dependent vasodilator responses to methacholine become severely impaired as a consequence of balloon catheter injury followed by intimal hyperplasia. However, these pharmacological responses may fully recover upon a prolonged period of endothelial regeneration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005147
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    U-83836E prevents kainic acid-induced neuronal damage (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 413-418 
    Details
    ISSN: 1432-1912
    Keywords: Key words PBR ; Kainate ; Reactive oxygen species ; Glutamate ; U-83836E ; Mitochondria ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of kainic acid (KA) on mitochondrial membrane potential (MMP) and reactive-oxygen species (ROS) production was studied in dissociated cerebellar granule cells from rat pups. KA induced a maximum increase of 361%±35% in ROS production. The lazaroid compound U-83836E (at concentrations ranging from 10–9 to 5×10–6M) completely inhibited this increase, with an IC50 value of 3.02±1.08×10–7M. KA also decreased the mitochondrial membrane potential (MMP), with a maximum decrease of about 30%. Absence of Na+ in the incubation medium did not significantly alter the effect of KA on MMP. As expected, the AMPA/kainate receptor antagonist NBQX inhibited the effects of KA on MMP with an IC50 value of 1.1±0.8μM. However, the lazaroid U-83836E, indomethacin, nor-dihydroguaiaretic acid and L-nitroarginine all failed to inhibit the KA-induced decrease in the MMP. Finally, to assess the neuroprotective effect of U-83836E on KA-induced neurotoxicityin vivo, the increase in the peripheral-type benzodiazepine receptor density in rat hippocampus was measured. Treatment with KA increased the Bmax to 1341±192fmol mg–1. When U-83836E was coadministered with KA, the Bmax was reduced to 765±122fmol mg–1, which was not significantly different from the Bmax obtained from untreated rats (Bmax: 518±33fmol mg–1). We conclude that treatment with the lazaroid U-83836E might be a suitable therapeutic strategy in neurodegenerative disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005187
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    Investigation of the influence of pregnancy on the role of nitric oxide in gastric emptying and non-adrenergic non-cholinergic relaxation in the rat (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 671-676 
    Details
    ISSN: 1432-1912
    Keywords: Key words Gastric emptying ; Nitric oxide ; Pregnancy ; Gastric fundus ; Pylorus ; Non-adrenergic non-cholinergic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of pregnancy on the role of nitric oxide (NO) in gastric emptying and in non-adrenergic non-cholinergic (NANC) relaxation was studied in rats. The gastric emptying of a non-nutrient liquid solution and of polysterene beads was studied in non-pregnant (NP), 6 to 7 days pregnant (P7) and 18 to 20 days pregnant (P20) rats. Longitudinal muscle strips of the gastric fundus and circular muscle strips of the pylorus were isolated from NP and P20 rats and NANC relaxations were induced by electrical field stimulation. The gastric emptying of the liquid meal was significantly increased in P20 rats as compared to NP and P7 rats. In NP rats, NG-nitro-L-arginine methyl ester (L-NAME) dose-dependently (50–150 mg/kg ip) reduced the gastric liquid emptying; the inhibitory effect of 100 mg/kg L-NAME ip was prevented by 400 mg/kg ip L-arginine and was mimicked by 100 mg/kg NG-monomethyl-L-arginine (L-NMMA). The percentage inhibition of the liquid emptying by L-NAME did not differ between the 3 groups, except for the dose of 150 mg/kg ip where it was significantly lower in P20 rats. The gastric emptying of beads was 54% in NP, 36% in P7 and 69% in P20 rats but these values were not significantly different illustrating the great variability. The inhibitory effect of L-NAME (25 and 100 mg/kg ip) on the emptying of beads did not differ between the 3 groups. As evaluated in NP rats, the inhibitory effect of L-NAME on the gastric emptying of the beads was not prevented by L-arginine nor mimicked by L–NMMA. Electrical field stimulation in NANC conditions induced frequency-dependent relaxations in the fundus strips and relaxations followed by rebound contractions in the pyloric strips. These electrically induced NANC relaxations and their reduction by 3×10–4 M L-NAME were not different between NP and P20 rats. It can be concluded that no evidence for a regulatory role of NO in the gastric emptying of the beads was found, and that the nitrergic contribution to the gastric emptying of liquids and to the fundic and pyloric NANC relaxations was not influenced by pregnancy in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005223
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    Oxytocin increases the survival of musculocutaneous flaps (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 701-704 
    Details
    ISSN: 1432-1912
    Keywords: Key words Oxytocin ; Rat ; Musculocutaneous flap ; Wound healing ; Oxytocin antagonist ; Growth factors ; IGF-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to evaluate the effect of oxytocin on survival of musculocutaneous flaps in male Sprague-Dawley rats. For this purpose oxytocin (0.1 or 1.0 mg/kg), an oxytocin antagonist (1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin) (1.0 mg/kg) alone or in combination with oxytocin (1.0 mg/kg) or saline was given subcutaneously (s.c.), 24 hours and 1 hour before and 24 hours after flap surgery. In addition, oxytocin (1 µg/kg) or saline was given intracerebroventricularly (i.c.v.) according to the same schedule. Six days after surgery the amount of viable tissue was measured. Oxytocin 1.0 (but not 0.1) mg/kg s.c. and 1.0 µg/kg i.c.v. increased survival of the flaps (s.c.: 13.8±14.6% versus 6.10±5.45%; p〈0.05 and i.c.v.: 25.5±14.0% versus 10.3±5.79%; p〈0.01). This effect was abolished by the oxytocin antagonist. Furthermore, the oxytocin-treated rats had significantly higher plasma levels of insulin-like growth factor-1 (IGF-1) (p〈0.05). These data indicate that oxytocin increases the survival of musculocutaneous flaps. The effect seems to be exerted within the central nervous system since a 1000 fold lower dose of oxytocin given i.c.v. increased flap survival to the same extent as the s.c. given dose. IGF-1 might be one of the mediators of this effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005227
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    Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in isolated rat lung and liver (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 336-343 
    Details
    ISSN: 1432-1912
    Keywords: Key words NNK ; Elimination kinetics ; Metabolism ; Perfusion ; Lung ; Liver ; Rat ; N-oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen in all species tested. To elicit its tumorigenic effects NNK requires metabolic activation which is supposed to take place via α-hydroxylation, whereas N-oxidation is suggested to be a detoxification pathway. The differences in the organ specific metabolism of NNK may be crucial for the organotropy in NNK-induced carcinogenesis. Therefore, metabolism of NNK was investigated in the target organ lung and in liver of Fischer 344 (F344) rats using the model of isolated perfused organs. High activity to metabolize 35 nM [5-3H]NNK was observed in both perfused organs. NNK was eliminated by liver substantially faster (clearance 6.9 ± 1.6 ml/min, half-life 14.6 ± 1.2 min) than by lung (clearance 2.1 ± 0.5 ml/min, half-life 47.9 ± 7.4 min). When the clearance is calculated for a gram of organ or for metabolically active cell forms, the risk with respect to carcinogenic mechanisms was higher in lung than in liver. The metabolism of NNK in liver yielded the two products of NNK α-hydroxylation, the 4-oxo-4-(3-pyridyl)-butyric acid (keto acid) and 4-hydroxy-4-(3-pyridyl)-butyric acid (hydroxy acid). In lung, the major metabolite of NNK was 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide). Substantial amounts of metabolites formed from methyl hydroxylation of NNK, which is one of the two possible pathways of α-hydroxylation, were detected in lung but not in liver perfusion. Formation of these metabolites (4-oxo-4-(3-pyridyl)-butanol (keto alcohol), and 4-hydroxy-4-(3-pyridyl)-butanol (diol) can give rise to pyridyloxobutylating of DNA. When isolated rat livers were perfused with 150 μM NNK, equal to a dosage which is sufficient to induce liver tumors in rat, glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was increased when compared to the concentration of 35 nM NNK. Nevertheless, the main part of NNK was also transformed via α-hydroxylation for this high concentration of NNK.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005176
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    Rat models of normocalcemic hypercalciuria of different pathogenic mechanisms (1998)
    Springer
    Pediatric nephrology 12 (1998), S. 201-205 
    Details
    ISSN: 1432-198X
    Keywords: Key words: Hypercalciuria ; Idiopathic hypercalciuria ; 1 ; 25-Dihydroxyvitamin D ; Furosemide ; Ammonium chloride ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Hypercalciuria was induced in female Sprague-Dawley rats, aged 40±2 days, by 7-day administration (mean±SEM) of calcitriol (5.4±0.1 ng/100 g per day, intraperitoneal), furosemide (14.9±1.9 mg/100 g per day, oral), or ammonium chloride (3.8±0.1 mEq/100 g per day, oral). Calciuria increased from 1.9±0.2, 1.6±0.2, and 1.9±0.3 to 5.4±0.5, 4.0±0.9, and 5.4±0.5 mg/100 g per day in the calcitriol (VD, n = 9), furosemide (F, n = 6), and ammonium chloride (AC, n = 10) groups, respectively. Calciuria did not change (1.9±0.3 vs. 1.6±0.1 mg/100 g per day) in control rats (n = 8). Ninety-six percent of treated rats became hypercalciuric as assessed by urine calcium excretion above the 90th percentile of normal values. Hypercalciuria was of similar degree in the three groups of rats and was not associated with hypercalcemia, metabolic acidosis, severe serum electrolyte imbalance, or growth impairment. VD rats had low serum parathyroid hormone (PTH) concentrations (3.0±0.5 pg/ml vs. 15.8±1.3 pg/ml in controls, P 〈0.05), whereas serum PTH was not significantly elevated in F rats (16.2±1.8 pg/ml). Thus, the protocol caused three forms of hypercalciuria that mimicked the clinical conditions of idiopathic hypercalciuria in humans and may clearly be differentiated according to their mechanism of production. This experimental model of normocalcemic hypercalciuria may be useful to clarify unknown aspects of pathogenesis and pathophysiology of idiopathic hypercalciuria in children.
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    URL: http://dx.doi.org/10.1007/s004670050437
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    Discriminative stimulus properties of mCPP: evidence for a 5-HT2C receptor mode of action (1998)
    Springer
    Psychopharmacology 137 (1998), S. 292-302 
    Details
    ISSN: 1432-2072
    Keywords: Key words mCPP (m-chlorophenylpiperazine) ; Drug discrimination ; 5-HT2C ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous drug discrimination studies with the serotonergic drug m-chlorophenylpiperazine (mCPP) showed conflicting results, with some authors concluding that the cue was mediated by 5-HT2C receptors, but others that it was definitively not. We further examined the discriminative stimulus properties of mCPP in rats and reviewed previously published data. We trained rats to discriminate mCPP (2.0 mg/kg, PO) from water. We found that the mCPP cue generalized to m-trifluoromethyl-phenylpiperazine (TFMPP) and 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), and partially to eltoprazine, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), fenfluramine and trazodone. A moderate level of generalization was obtained with quipazine, 1-(m-chlorophenyl)biguanide and clonidine. No generalization was found with flesinoxan, methiothepin, idazoxan and haloperidol. Mianserin and methysergide antagonized the mCPP stimulus, whereas ketanserin antagonized it partially. Metergoline, methiothepin and clozapine only marginally antagonized the mCPP stimulus. These results show that the discriminative stimulus effects of mCPP are predominantly mediated by 5-HT2C receptors, and to some extent by 5-HT1B receptors. When considering our results and other research together, the substitution tests clearly point to a 5-HT2C receptor mediated stimulus, with an additional role for 5-HT1B receptors. Antagonism studies are less clearcut, but are also suggestive of a 5-HT2C receptor mediated effect. A definitive answer as to whether other receptors, e.g. 5-HT2B and 5-HT7, are of any importance in mCPP’s discriminative stimulus properties has to wait for more selective ligands.
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    URL: http://dx.doi.org/10.1007/s002130050622
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    Neonatal clomipramine treatment, alcohol intake and circadian rhythms in rats (1998)
    Springer
    Psychopharmacology 138 (1998), S. 176-183 
    Details
    ISSN: 1432-2072
    Keywords: Key words Alcohol ; Antidepressant ; Circadian ; Clomipramine ; Neonatal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neonatal exposure to antidepressant monoamine re-uptake inhibitors produces a wide variety of effects on the behavior and physiology of adult rats which are consistent with features of clinical depression. Since depressed patients show characteristic alterations in circadian rhythmicity, our laboratory has examined free-running circadian drinking rhythms in this putative animal depression model. Previously, neonatal desipramine treatment was shown to lengthen free-running period, and increase circadian amplitude, spectral magnitude, and voluntary alcohol intake (10% ethanol v/v) of male rats. The purpose of the present study was to examine the effects of neonatal clomipramine treatment (25 or 30 mg/kg SC, postnatal days 8–21) on circadian drinking rhythms and alcohol intake of both male and female rats. In addition, effects of alcohol exposure on circadian rhythmicity were also examined. Contrary to expectations, free-running period of clomipramine-treated rats did not differ from saline-treated controls in either constant darkness (DD) or constant light (LL), but spectral magnitude was increased in clomipramine-treated males and females, and circadian amplitude was increased in clomipramine-treated females. Neonatal clomipramine also increased voluntary alcohol intake, and both clomipramine- and saline-treated groups displayed significant period-shortening during alcohol exposure. Taken together, these results suggest that alterations in the amplitude and coherence of circadian rhythmicity may be more consistent than alterations in free-running period in animal depression models, as has been suggested previously for depressed patients.
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    URL: http://dx.doi.org/10.1007/s002130050660
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    Activation of midline thalamic nuclei by antipsychotic drugs (1998)
    Springer
    Psychopharmacology 135 (1998), S. 37-43 
    Details
    ISSN: 1432-2072
    Keywords: Key wordsNeuroleptics ; Antipsychotic drugs ; Thalamus ; Fos immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The thalamus has been proposed as a site which may be involved in the production of the syndrome of schizophrenia and the response of schizophrenic symptoms to treatment. These studies test whether, consistent with this hypothesis, the activation of thalamic nuclei is a shared property of neuroleptic antipsychotic drugs. Rats were given single doses of the typical high and low potency neuroleptics haloperidol (1 mg/kg) and chlorpromazine (20 mg/kg), the atypical neuroleptics thiroridazine (20 mg/kg) and clozapine (20 mg/kg), the specific dopamine antagonist raclopride (3 mg/kg), the mixed dopamine/serotonin antagonist risperidone (3 mg/kg) or drug-free vehicle. Increased expression of Fos-like protein was utilized as a marker of cellular activation. All drugs tested, including typical and atypical antipsychotic agents, led to similar effects on the midline thalamic paraventricular, centromedian and rhomboid nuclei and the nucleus reuniens. These results suggest that midline thalamic nuclei may participate in neural circuits mediating some of the shared effects of antipsychotic drugs.
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    URL: http://dx.doi.org/10.1007/s002130050483
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    Ethanol and N-methyl-D-aspartate receptor complex interactions: a detailed drug discrimination study in the rat (1998)
    Springer
    Psychopharmacology 135 (1998), S. 44-51 
    Details
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Rat ; Ethanol ; NMDA receptor ; AMPA receptor ; Dizocilpine ; Memantine ; Phencyclidine ; N-allyl-normetazocine ; Pentazocine ; Arcaine ; Polyamine site ligand ; Glycine site ligand
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus properties of compounds that interact with the NMDA receptor complex were investigated in rats trained to discriminate ethanol from saline. Male Wistar rats were trained in a two-lever operant drug discrimination paradigm to make differential responses [fixed ratio 10 (FR10)] for food after ethanol (1 g/kg IP; 12% v/v ethanol solution) and saline vehicle injections. Drug effects were assessed by means of generalization and antagonism tests. In the generalization tests, the noncompetitive NMDA antagonists acting at the ion channel dizocilpine, memantine, phencyclidine (PCP) and the sigma1 receptor agonists (+)-pentazocine and (+)-N-allyl-normetazocine (NANM) dose-dependently generalized for ethanol, whereas the α-amino-3-hydroxy- 5-methyl-4-isoxazole-propionate (AMPA) antagonist GYKI 52466, the glycine antagonists L-701,324 and MRZ 2/502, the polyamine site antagonist arcaine and the polyamine site ligand spermidine, did not. Our results show that the noncompetitive NMDA antagonists fully substitute dose-dependently for ethanol in a drug-discrimination task. The ethanol-like discriminative stimulus effects of PCP, pentazocine and NANM, which are also sigma receptor ligands, are likely to be attributed to their activity at NMDA receptors. We therefore assume that some of the acute effects of ethanol are mediated via NMDA receptor antagonism at the PCP binding site.
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    URL: http://dx.doi.org/10.1007/s002130050484
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    Acquisition of nicotine self-administration in rats: the effects of dose, feeding schedule, and drug contingency (1998)
    Springer
    Psychopharmacology 136 (1998), S. 83-90 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Self-administration ; Dose ; Contingency ; Yoking ; Feeding ; Rat ; Sprague-Dawley
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The studies presented here were designed to further clarify the nature of nicotine self-administration (SA) based on a limited access model in which rats are food restricted, receive operant training using food reinforcement, and are then tested in daily 1-h drug sessions. We examined the effects of dose, feeding schedule, and contingency of drug delivery on acquisition of nicotine SA. Two doses of nicotine bitartrate, 0.03 and 0.06 mg/kg per infusion (free base), supported the transition from food-reinforced to drug-reinforced responding, although the pattern of behavior differed between these doses. In contrast, 0.01 mg/kg per infusion failed to maintain nicotine SA. In a second study, animals were divided into three groups according to feeding schedule. Rats that were both weight restricted and food deprived showed the highest level of SA behavior, although neither food deprivation nor weight restriction was necessary to establish SA. In the third experiment, rats that were switched from food to nicotine as the response-dependent reinforcer maintained higher response rates throughout a 9-day period than animals switched to response-independent (i.e., yoked) nicotine which showed minimal responding after day 1. Furthermore, the differences between self-administering and yoked animals emerged during the first session, suggesting that nicotine may serve as a reinforcer during the first drug exposure in naive animals. These results indicate that acquisition of nicotine SA can be influenced by both dose of nicotine and feeding schedule and that, in animals previously trained on a food-reinforced operant, active lever pressing is maintained only when nicotine delivery is contingent upon responding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050542
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  • 87
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    Lack of sensitization to the effects of d-amphetamine and apomorphine on sensorimotor gating in rats (1998)
    Springer
    Psychopharmacology 135 (1998), S. 296-304 
    Details
    ISSN: 1432-2072
    Keywords: Key words Prepulse inhibition ; Sensorimotor gating ; Sensitization ; Locomotor activity ; Amphetamine ; Apomorphine ; Schizophrenia ; Startle ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study assessed whether repeated injections of d-amphetamine or apomorphine could induce sensitization to the disruptive effects of these psychomotor stimulants on sensorimotor gating in rats. In the first experiment, rats were given six pre-exposures to either 2.0 mg/kg d-amphetamine or saline before being tested for the effects of d-amphetamine (0.0, 0.5, 1.0, 2.0 or 4.0 mg/kg, IP) on prepulse inhibition of acoustic startle (PPI) and locomotor activity. The tests for PPI confirmed that sensorimotor gating could be disrupted by a high dose of d-amphetamine (4.0 mg/kg). However, comparison of the dose-response curves for the drug and saline pre-exposed groups did not reveal evidence for sensitization to this d-amphetamine effect in drug-pre-exposed rats, despite indications that sensitization had developed to the locomotor stimulant effects of d-amphetamine. A similar pattern of results was obtained in a second experiment that examined the effects of apomorphine (0.0, 0.1, 0.2, 0.4 and 0.8 mg/kg, SC) on PPI and locomotion in rats pre-exposed to 2.0 mg/kg of this drug or its vehicle. These findings demonstrate that treatments which induce sensitization to the behavioral activating effects of psychomotor stimulants do not necessarily produce sensitization to the disruptive effects of stimulants on sensorimotor gating. The implications of these results for hypotheses linking sensitization-like processes to the etiology of schizophrenia are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050513
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  • 88
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    Repeated administration of ephedrine induces behavioral sensitization in rats (1998)
    Springer
    Psychopharmacology 140 (1998), S. 52-56 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Dopamine ; Ephedrine ; Locomotion ; Rat ; Sensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Systemic injection of the sympathomimetic agent ephedrine (EPH) stimulates locomotion in drug-naive rats, an effect that may be dependent on the enantiomer of EPH employed [(–)-EPH or (+)-EPH]. The present experiments examined the effects of repeated EPH exposure on locomotion in rats to assess whether these treatments result in drug tolerance or sensitization. In experiment 1, adult male rats were injected once daily with 0, 10, 20, or 40 mg/kg (–)-EPH (IP) on each of 11 days. Locomotor activity was assessed for 60 min after drug injection. Acute exposure to (–)-EPH treatment increased locomotion for animals receiving 20 or 40 mg/kg, and this effect was augmented after 11 days of drug administration. A vehicle-only injection was given to all animals on day 12 to determine the influence of environmental cues on sensitization. On day 13, all rats were injected with 10 mg/kg cocaine HCl to assess whether repeated (–)-EPH exposure produced a cross-sensitization to cocaine (10 mg/kg, IP). Only rats treated repeatedly with 40 mg/kg (–)-EPH exhibited increases in cocaine-stimulated locomotion relative to saline-treated rats. In experiment 2, repeated exposure to (+)-EPH, 40 mg/kg, but not 20 mg/kg, increased activity and demonstrated the development of sensitization. Cross-sensitization to cocaine (10 mg/kg, IP) was not evident following treatment with either concentration of (+)-EPH. There was no evidence that contextual events alone played a role in the effects observed here.
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    URL: http://dx.doi.org/10.1007/s002130050738
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  • 89
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    Electronic Resource
    Tolerance and cross-tolerance to the rate-suppressing effects of opioids in butorphanol-treated rats: influence of maintenance dose and relative efficacy at the mu receptor (1998)
    Springer
    Psychopharmacology 140 (1998), S. 57-68 
    Details
    ISSN: 1432-2072
    Keywords: Key words Butorphanol ; Cross tolerance ; Dependence ; Relative efficacy ; Opioid ; Rat ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of the present investigation was to examine the development of tolerance to the rate-suppressing effects of mu and kappa opioids in rats administered either 3.0 (low) or 30 (high) mg/kg per day of butorphanol, an opioid with low relative efficacy at the mu receptor. The mu opioids butorphanol, buprenorphine, morphine, fentanyl and sufentanil, and the kappa opioid U50,488 dose-dependently suppressed responding under all conditions examined. In rats administered the low maintenance dose of butorphanol, tolerance developed to the effects of butorphanol, buprenorphine and morphine, but not to fentanyl and sufentanil. In rats administered the high maintenance dose, tolerance developed to all of the mu opioids examined. In both treatment groups, the degree to which tolerance developed was greater for butorphanol and buprenorphine than for morphine, fentanyl and sufentanil; and the degree to which tolerance developed to these mu opioids was greater in rats administered the high maintenance dose of butorphanol. The tolerance that developed to morphine, fentanyl and sufentanil was not altered when tested at both 23 and 47 h following the previous maintenance dose of butorphanol, suggesting that these changes were not due to any acute pharmacological interactions between butorphanol and the test compound (i.e., antagonism). Tolerance was also conferred to the kappa opioid U50,488 in both groups of rats, and in rats administered the high maintenance dose, this effect was obtained when tested 23 and 47 h following the previous maintenance dose of butorphanol. Physical dependence developed in rats administered the high maintenance dose of butorphanol, as evidenced by the development of enhanced sensitivity to the rate-suppressing effects of naloxone, and the finding that 30 mg/kg naloxone decreased body weight in a time-dependent manner. No physical dependence was apparent in rats administered the low maintenance dose of butorphanol. These data suggest that during chronic treatment with butorphanol, (1) greater degrees of tolerance are conferred to drugs possessing low efficacy at the mu opioid receptor, (2) tolerance is enhanced as the maintenance dose of the toleragen is increased, and (3) mu-opioid tolerance may be observed under conditions that do not produce mu-opioid dependence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050739
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  • 90
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    Haloperidol, raclopride, and eticlopride induce microcatalepsy during operant performance in rats, but clozapine and SCH 23390 do not (1998)
    Springer
    Psychopharmacology 140 (1998), S. 81-90 
    Details
    ISSN: 1432-2072
    Keywords: Key words Neuroleptics ; Dopamine receptor ; Catalepsy ; EPS ; Antipsychotic drug ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of this work was (1) to assess the ability of selected antipsychotic and comparison drugs to induce arrest of movement phenomena during operant responding and (2) to evaluate the capacity of muscarinic anitcholinergics to block such effects. The effects of haloperidol (0.02–0.12 mg/kg, IP, 45 min), raclopride (0.05–0.80 mg/kg, IP, 30 min) eticlopride (0.02–0.16 mg/kg, IP, 45 min), clozapine (1.0–8.0 mg/kg, IP, 60 min) and SCH 23390 (0.01–0.16 mg/kg, IP, 30 min) were administered to rats for 4 weeks in a between-groups dosing design. Operant responses in 15 min and the maximum duration of the rat’s muzzle entry into the reinforcement dipper well (the measure of arrest of movement that reflected microcatalepsy) were the quantitative measures of behavior. The D2 antagonists dose-relatedly decreased operant responding and increased maximum muzzle duration, effects that were significantly reversed by the anticholinergic scopolamine (0.1 mg/kg) or atropine (6.0 mg/kg). Although the atypical antipsychotic drug clozapine and the selective D1 antagonist SCH 23390 both significantly reduced operant responding, these drugs did not produce microcatalepsy. The results suggested that microcatalepsy expressed in the context of ongoing operant behavior may model low-dose extrapyramidal side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050742
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  • 91
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    Electronic Resource
    Evidence that GABA transmission mediates context-specific extinction of learned fear (1998)
    Springer
    Psychopharmacology 140 (1998), S. 105-115 
    Details
    ISSN: 1432-2072
    Keywords: Key words FG 7142 ; β-Carboline ; Benzodiazepine inverse agonist ; Latent inhibition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Six experiments used rats to study the effects of the β-carboline FG 7142 on extinction of fear responses (freezing) to an auditory cue that had signalled footshock. Subcutaneous injection of FG 7142 interfered with the development of extinction without having any detectable effect on the rats’ levels of fear prior to extinction. Injection of FG 7142 also reversed extinction, partially reinstating fear responses that had been extinguished previously. A similar reinstatement of extinguished fear was seen when rats were tested for fear of the cue in a different chamber. The reinstatement produced by FG 7142 and that caused by context shift were not additive: FG 7142 did not increase extinguished fear if rats were tested in the different chamber. Finally, FG 7142 had no detectable effect on the latent inhibition of fear produced by repeatedly presenting the cue alone before conditioning with shock, even though this inhibition, like extinction, was affected by a shift in context. The present findings indicate that GABA transmission at GABAA receptors is involved in the inhibition of extinguished fear, and that this effect of GABA is regulated by those cues that constitute the extinction context.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050745
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  • 92
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    Preclinical evaluation of the reinforcing and discriminative stimulus effects of agomelatine (S-20098), a melatonin agonist (1998)
    Springer
    Psychopharmacology 140 (1998), S. 503-509 
    Details
    ISSN: 1432-2072
    Keywords: Key words Agomelatine ; S-20098 ; Melatonin ; Diazepam ; Methohexital ; Drug discrimination ; Self-administration ; Substance abuse evaluation ; Monkey ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Agomelatine (S-20098), an analog of melatonin, has shown promise as a chronobiotic in animal models of sleep phase disorders and is being developed for clinical use. Previous research has shown that the pharmacological profile of melatonin-like drugs overlaps that of γ-amino butyric acid (GABA) agonists. Given the potential of drugs within the latter class for recreational abuse in humans, evaluation of this potential for melatonin analogs that target similar therapeutic indications is important. In the present study, agomelatine was tested in animal models of the subjective and reinforcing effects of CNS depressant drugs; i.e., diazepam discrimination in rats and IV methohexital self-administration in rhesus monkeys, respectively. Neither agomelatine nor melatonin substituted for diazepam in rats trained to discriminate 2.5 mg/kg diazepam from vehicle. Further, agomelatine was not self-administered by rhesus monkeys. These results suggest that agomelatine would not produce diazepam-like intoxication in humans, nor would it likely be subject to abuse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050795
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  • 93
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    The development of addiction to d-amphetamine in an animal model: same principles as for alcohol and opiate (1998)
    Springer
    Psychopharmacology 140 (1998), S. 510-518 
    Details
    ISSN: 1432-2072
    Keywords: Key words Animal model ; Addiction ; Loss of control ; Dependence ; Withdrawal ; d-Amphetamine ; Opiate ; Alcohol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37 ± 0.02 mg/kg per day, subordinate rats: 0.57 ± 0.05 mg/kg per day) and environmental variables (group housing: 0.21 ± 0.02 mg/kg per day, single housing: 0.41 ± 0.03 mg/kg per day). Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9 ± 0.2 mg/kg per day in week 47), although the experimental conditions remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6 ± 0.6 mg/kg per day; age-matched controls: 0.37 ± 0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1 ± 0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42 ± 0.04 mg/kg per day). Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol and opiates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050796
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  • 94
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    Δ9-THC training dose as a determinant for (R)-methanandamide generalization in rats (1998)
    Springer
    Psychopharmacology 140 (1998), S. 519-522 
    Details
    ISSN: 1432-2072
    Keywords: Key words Δ9-THC ; Cannabinoids ; (R)-methanandamide ; Anandamides ; Efficacy ; Drug discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The objective of this study was to examine if (R)-methanandamide, a metabolically stable chiral analog of the endogenous ligand anandamide, is a cannabimimetic with a lower efficacy than Δ9-THC. Employing a two-lever choice drug discrimination procedure, rats were trained to discriminate between 1.8, 3.0, or 5.6 mg/kg Δ9-tetrahydrocannabinol (Δ9-THC) and vehicle. Different training doses were used in order to create assays with different efficacy demands. Generalization tests with 18 mg/kg (R)-methanandamide yielded around 90% Δ9-THC responses in the two lower Δ9-THC training dose conditions. However, only around 60% Δ9-THC responses occurred in the 5.6 mg/kg Δ9-THC training dose condition in tests with 18 mg/kg (R)-methanandamide; a higher dose (30 mg/kg) produced even fewer Δ9-THC-appropriate responses in this group. Morphine did not substitute for Δ9-THC. In conclusion, the data with Δ9-THC and (R)-methanandamide indicate that cannabinoid agonists can have varying degrees of intrinsic activity at a receptor site, or may produce their behavioral actions through multiple mechanisms, or both.
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    URL: http://dx.doi.org/10.1007/s002130050797
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  • 95
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    Electronic Resource
    Prevention of lithium nephrotoxicity in a novel one-hour model in rats (1998)
    Springer
    Psychopharmacology 138 (1998), S. 34-39 
    Details
    ISSN: 1432-2072
    Keywords: Key words Lithium ; Nephrotoxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is well established that lithium can cause morphologically visible damage to the kidneys of humans and animals. Although the clinical significance of its nephrotoxicity is debatable, it would be desirable to find a method to prevent lithium’s effect on the kidneys. Toward this end, we have developed a novel method for producing nephrotoxicity that will be useful for research on prevention. A single, large, toxic dose of lithium chloride (LiCl) caused necrosis of the distal convoluted tubules, which was visible by light microscopy in 30 min, had fully developed in 1 h, and had disappeared by the next day. The lesions were seen after IP or IV injections of fasted rats of three different strains. Equivalent doses of NaCl, KCl, MgCl2 and combinations thereof had no such effect, nor did they inhibit nephrotoxicity when incorporated into the LiCl solution. However, relatively small doses of LiCl injected by any route 3 or 24 h beforehand prevented the nephrotoxicity. The mechanism of prevention is not known, but it does not involve reduction of lithium levels in the kidneys.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050642
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  • 96
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    Repeated tail pinch leads to desensitization of postsynaptic α2-adrenoceptors which modulate the jaw-opening reflex in the rat (1998)
    Springer
    Psychopharmacology 138 (1998), S. 96-101 
    Details
    ISSN: 1432-2072
    Keywords: Key words Jaw-opening reflex ; α2-Adrenoceptor sensitivity ; Tail pinch ; Repeated stress ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There are few in vivo studies which have investigated the modulation of central postsynaptic α 2-adrenoceptors functionality provoked by stress. We assessed in the rat the effects of either single or repeated tail pinch on clonidine-induced inhibition of the jaw-opening reflex (JOR) via activation of postsynaptic central α 2-adrenoceptors. At the end of each experimental period, the progressive inhibition of the digastric electromyographic responses elicited by orofacial electrical stimulation after the IV administration of cumulative doses (× 3.3) of clonidine (0.1–10 000 μg/kg) was recorded. Single tail pinch did not significantly modify the ability of the agonist to inhibit the JOR, although there was a tendency to decrease the basal amplitude of the reflex (a 40% reduction) immediately after exposure to the single stressor. However, the dose-response curve for clonidine-induced inhibition of the JOR was clearly shifted to the right in rats exposed to repeated tail pinch (ED50 was increased by 152%, P 〈 0.0001) when compared with the unstressed control group, without affecting the slope of the inhibitory function and the estimated maximum effect for the agonist. These results show that repeated stress leads to a subsensitivity of the α 2-adrenoceptors which modulate the JOR, suggesting the development of adaptive mechanisms in postsynaptic α 2-adrenoceptors in response to stress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050650
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  • 97
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    Evidence for behavioral sensitization to cocaine in preweanling rat pups (1998)
    Springer
    Psychopharmacology 138 (1998), S. 114-123 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Behavioral sensitization ; Ontogeny ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While chronic intermittent administration of stimulants often induces behavioral sensitization in adulthood, stimulant sensitization has rarely been reported prior to weaning [around postnatal day (P) 21]. Consistent pairing of drug administration with the test context often facilitates sensitization in adults, yet young animals have been typically returned to the home cage immediately post-injection. To determine whether promoting context-dependent sensitization might facilitate expression of sensitization in preweanlings, Sprague-Dawley rats were injected daily from P14 to P20 with 0, 5, 15, or 30 mg/kg cocaine HC1 and placed for 30 min in either the experimental chamber or home cage. On P21 (test day), subjects were challenged with either 15 mg/kg cocaine or saline prior to placement in the experimental chamber. Significant sensitization of cocaine-induced stereotyped head movements was evident in animals given 15 or 30 mg/kg chronically in the experimental chamber, but not when these same doses were given in the home cage. Less consistent evidence for cocaine-induced sensitization was seen when examining locomotion, although trends for sensitization of this behavior were seen in animals chronically injected in either the test chamber or home cage. Thus, preweanlings can exhibit cocaine sensitization, particularly in terms of stereotypy, when tested shortly after the chronic exposure period, with expression of this sensitization being facilitated by pairing the chronic injections with the test context.
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    URL: http://dx.doi.org/10.1007/s002130050653
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  • 98
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    Sabcomeline (SB-202026), a functionally selective M1 receptor partial agonist, reverses delay-induced deficits in the T-maze (1998)
    Springer
    Psychopharmacology 138 (1998), S. 275-282 
    Details
    ISSN: 1432-2072
    Keywords: Key words Alzheimer’s disease ; T-maze ; Conditioned taste aversion ; Muscarinic agonists ; Sabcomeline ; SB-202026 ; THA ; RS86 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Sabcomeline, (SB-202026 [R-(Z)-α-(methoxyimino)-1-azabicyclo [2.2.2] octane-3-acetonitrile]), a functionally selective muscarinic M1 receptor partial agonist, was tested in rats trained to perform a delayed, reinforced alternation task in a T maze, a test of short-term spatial memory. For comparison the cholinesterase inhibitor tacrine (THA-9-amino-1,2,3,4-tetrahydroaminoacridine) and the non-selective muscarinic receptor agonist RS86 (2-ethyl-8-methyl-2,8 diazospiro [4.5]-decane-1,3-dione hydrobromide) were also tested and all three compounds were also compared using a conditioned taste aversion (CTA) task. Sabcomeline (0.001–1.0 mg/kg IP) significantly reversed the T-maze choice accuracy deficit induced by a 20-s delay at 0.03 and 0.1 mg/kg. RS86 (0.1–3.0 mg/kg IP) reversed the deficit at 1.0 mg/kg and THA (0.1–3.0 mg/kg IP) had no effect at any dose. All three compounds induced conditioned taste aversion with minimum effective doses (MED) of 0.3, 1.0 and 3.0 mg/kg, respectively. The results show that sabcomeline reverses delay induced deficits in T-maze choice accuracy in a rewarded alternation task at doses approximately 10 times lower than those required to induce conditioned taste aversion. RS86 was equipotent in both tests. These data support the findings of clinical studies which have shown that SB-202026 provides significant symptomatic improvement in patients with probable Alzheimer’s disease at doses which do not induce cholinergic side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050672
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  • 99
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    The pharmacology of impulsive behaviour in rats III: the effects of amphetamine, haloperidol, imipramine, chlordiazepoxide and ethanol on a paced fixed consecutive number schedule (1998)
    Springer
    Psychopharmacology 138 (1998), S. 295-304 
    Details
    ISSN: 1432-2072
    Keywords: Key words Impulsivity ; Rat ; Imipramine ; Ethanol ; Haloperidol ; Chlordiazepoxide ; Amphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The behavioural trait of impulsivity may be made up of different components, including rapid decision making, intolerance to the delay of reward and a tendency to terminate chains of responses prematurely. It has been proposed to measure the last of these in rats using fixed consecutive number (FCN) schedules. The present study uses a modified version of the FCN procedure in which responding was paced by retracting the response lever for short periods between presses. In this way, the experimenter could control the maximum rate of responding. The procedure was made up of two components based on an FCN 8 schedule of food reinforcement. In the Fast component, lever presses were spaced by a minimum of 2 s and in the Slow component by a minimum of 5 s. The average chain length was significantly shorter, and the rats were less efficient in the Slow component. Five drugs were tested on this baseline, imipramine (1.0–10.0 mg/kg), ethanol (300–3000 mg/kg administered PO), haloperidol (0.01–0.1 mg/kg), chlordiazepoxide (1.0–10.0 mg/kg) and d-amphetamine (0.2–0.8 mg/kg). All the drugs reduced responding at the highest dose, but imipramine was different from the others in that it increased the average number of responses in the chain and produced a shift in the chain length distribution to the right, possibly reflecting a reduction in impulsivity. The other four drugs reduced chain length at the highest dose, although in the case of ethanol this effect was very small and, unlike the other three drugs, did not result in a shift in the distribution to the left. The paced FCN procedure can differentiate the effects of different drugs on one aspect of impulsivity, and is likely to be a useful procedure for further study of this aspect of behaviour.
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    URL: http://dx.doi.org/10.1007/s002130050674
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  • 100
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    The pharmacology of impulsive behaviour in rats II: the effects of amphetamine, haloperidol, imipramine, chlordiazepoxide and other drugs on fixed consecutive number schedules (FCN 8 and FCN 32) (1998)
    Springer
    Psychopharmacology 138 (1998), S. 283-294 
    Details
    ISSN: 1432-2072
    Keywords: Key words Impulsivity ; Amphetamine ; Antidepressant ; Haloperidol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effects of drugs on one aspect of impulsive behaviour were evaluated using a schedule in which rats were trained to complete a fixed consecutive number of responses on one of two levers before pressing the second to obtain a reinforcer (FCN). Terminating the chain before completing the FCN resulted in the omission of the food, and can be considered an impulsive decision. Two groups of food-deprived rats were trained to press either 8 or 32 times on the left lever (FCN lever) of a two lever operant chamber before pressing the right lever (Reinforcement lever) to deliver a food pellet. Responding on the Reinforcement lever before completion of the sequence resulted in a short time-out and the rat had to begin the sequence again. After responding had stabilised, the rats were treated with a range of doses of a number of drugs. Impulsivity was assessed by several measures, including the mean chain length and the proportion of chains terminating in food delivery, and the distribution of chain lengths was analysed. The efficiency of the rats was similar under both FCN 8 and FCN 32, although it was more difficult to maintain a consistent baseline under FCN 32. Under the FCN 8 schedule, significant decreases in chain length were obtained with d-amphetamine (0.8–2.4 mg/kg), haloperidol (0.1 mg/kg), ethanol (1 and 3 g/kg) and chlordiazepoxide (10.0 mg/kg), and there were alterations in other measures consistent with an increase in impulsivity. Imipramine (1–10 mg/kg), citalopram (1–10 mg/kg) and metergoline (0.3–3.0 mg/kg) had no effect on mean chain length, although the first two drugs shifted the chain length distribution to the left. d-Amphetamine (0.4–1.2 mg/kg) and PCPA (100 mg/kg) reduced chain length and had other effects consistent with increased impulsivity under FCN 32 schedule, whereas imipramine had little, and citalopram no, effect. Taken generally, effect of the active drugs was relatively non-specific, including both a reduction in response rate and alterations in choice measures proposed to reflect an increase in impulsivity. Detailed analysis of the effect of amphetamine revealed that three processes were at work: chain shortening, an increased preference for the lever most closely associated with food delivery, and a gradual shift in the control over responding from the response sequence (pattern) to the individual lever press (act).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050673
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