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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 176 (1987), S. 303-311 
    ISSN: 1432-0568
    Keywords: Nonspecific cholinesterase ; Neural crest ; Mandibular process ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cholinergic traits in rat mandibular processes were examined histochemically, under the electron microscope, scope, at early developmental stages (Stages 20 to 23, by Christie's nomenclature). The histochemical reaction for detection of enzymes was performed by the thiocholine method. Nonspecific cholinesterase (EC 3.1.1.8) activity was found in ectomesenchymal cells, vascular endothelial cells, and in some epidermal cells at stages 20 and 21. The enzymatic activity was localized in the perinuclear and endoplasmic reticular cisternae. At stage 22, the number of cells with enzymatic activity decreased gradually, except in the case of the capillary endothelial cells. At stage 23, when the trigeminal nerve fiber was obvious in the mandibular processes, nonspecific cholinesterase activity was restricted to some of the endothelial cells and trigeminal ganglionic cells. In contrast, acetylcholinesterase activity was found on the membrane of trigeminal nerve fiber. Thus, the transient, nonspecific, cholinesterase activity, found in rat mandibular processes, may serve some functions in transmission, lipid metabolism or destruction of toxic cholinesters during the period that precedes organogenesis.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 176 (1987), S. 367-372 
    ISSN: 1432-0568
    Keywords: Cajal-Smirnow ansiform fibers ; Mossy fibers ; Axonal guidance ; Cerebellar cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present light and electron microscopic study deals with the morphology and organization of Cajal-Smirnow ansiform fibers (AFs) in the molecular layer of the cerebellar cortex. The cerebella of normal adult rats were processed with Cajal's reduced silver method and conventional electron microscopy. With the silver method AFs appear as isolated elements or, more frequently, as small bundles of myelinated fibers, which emerge from the medullary rays, ascend through the granular, Purkinje cell and molecular layers and curve back to reenter the granular layer or cerebellar white matter. They traced an arciform trajectory of variable width and height in the molecular layer. Relatively large bundles of AFs were rarely found. The occurrence of AFs was confirmed in semithin sections as myelinated fibers of variable diameter ranging from 1 to 6 μm. Oligodendrocytes were often observed near AFs. At the ultrastructural level, the most common type of AF is large, with a relatively thin myelin sheath and a moderately dense axoplasm. Nodal or terminal synaptic differentiations were not observed. We suggest that AFs are misoriented cerebellar mossy fibers and their occurrence may be the consequence of a small-scale error in the axonal guidance of growing mossy fibers.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 177 (1987), S. 183-188 
    ISSN: 1432-0568
    Keywords: Glia ; Cerebellum ; Rat ; Development ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bergmann glial (Golgi epithelial) cells in the cerebella of rats of various ages were stained by the rapid Golgi technique, and their radial stem processes were measured for length and diameter. Additionally, the average number of such processes per cell was counted, and the development of bushy lateral protrusions was quantified. The length of radial processes—depending on the thickness of the molecular layer—was found to increase up to the end of the 2nd year of life. This elongation was accompanied by a reduction of the mean process diameter which was, however, not sufficient to prevent an increase in the cytoplasmic volume of the elongating cells. A marked outgrowth of lateral protrusions was observed up to at least the 5th month of life. These data are compared with earlier findings on the development of rat brain stem fetal radial glia, and of rabbit retinal Müller cells. Common mechanisms of glial cell development are discussed.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 177 (1987), S. 37-49 
    ISSN: 1432-0568
    Keywords: Pudendal nerve ; Onuf's nucleus ; Spinal cord ; Rat ; HRP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Central distribution of efferent and afferent components of the pudendal nerve was examined in the rat by the horseradish peroxidase (HRP) method after HRP application to the central cut end of the pudendal nerve. The pudendal motoneurons were located in the dorsolateral, dorsomedial and lateral groups at L5 and L6. Each of the dorsolateral and dorsomedial groups constituted a slender longitudinal cell column. Pudendal motoneurons in the lateral group were scattered at L5, rostrodorsally to the dorsolateral group. The neurons in the dorsolateral and lateral groups were labelled with HRP applied to the nerve branch innervating the ischiocavernosus and sphincter urethrae muscles. The neurons in the dorsomedial group were labelled with HRP applied to the branch supplying the sphincter ani externus and bulbospongiosus muscles. Some dendrites of pudendal motoneurons in the dorsomedial group extended to the contralateral dorsomedial group. These crossing dendrites were observed not only in male rats but also in female. The average number of the pudendal motoneurons in the dorsolateral and dorsomedial groups were larger in male rats than in female. A few neurons of the intermediolateral nucleus at upper L6 were also labelled with HRP applied to the dorsalis penis (clitoridis) nerve. Axon terminals of the pudendal nerve were distributed, bilaterally with an ipsilateral predominance, to the gracile nucleus, as well as to the dorsal horn and dorsal commissural gray from L4 to S2. A few labelled axons were seen in the intermediolateral nucleus at L6 and S1. Axon terminals from the dorsalis penis nerve were distributed more medially in the dorsal horn than those from the perinealis nerve.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 175 (1987), S. 477-487 
    ISSN: 1432-0568
    Keywords: Cochlea ; Development ; SEM ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Maturation of the rat cochlea, from postnatal days 2 to 60, was studied using scanning electron microscopyt (SEM), with emphasis on stereocilia and tectorial membrane (TM). Two days after birth, the organ of Corti was very immature. An adult appearance of its surface was observed by day 16 in the basal turn, and by the end of the 3rd postnatal week in the apex. Stereocilia started their development first on inner hair cells. By contrast, the apical pole of outer hair cells ended its maturation before that of inner hair cells. Top-links were detected very early in inner hair cell stereociliary development (postnatal day 2). Marginal pillars temporarily attached the TM to the organ of Corti; they disappeared first in the apical region. This transient attachment seems to play a role in the coupling of outer hair cells to the TM, as prints of their longest stereocilia appeared at the undersurface of the TM by the same time. Moreover, these prints were more clear and regular at the base than at the apex of the cochlea. Results are discussed in relation to ultrastructural and functional data on rat cochlea maturation.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 72 (1987), S. 335-340 
    ISSN: 1432-0533
    Keywords: Glycogen ; Synapses ; Clarke's nucleus ; Nerve injury ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glycogen accumulation in the Clarke's nucleus neuropil of young adult rats whose sciatic nerves were crushed in the first postnatal day was investigated with the electron microscope. Glycogen was observed in synaptic boutons and in small myelinated axons. In some terminals, glycogen accumulated in membranebound structures resembling mitochondria and formed large multigranular bodies which were entirely separated from the axoplasm. The multigranular body reached the size of 1.3 μm. Glycogen was present as single beta particles of about 25–40 nm in diameter and in aggregations of large alpha clusters. The astrocytic glycogen distribution was almost similar to that of the control specimens. Glycogen was not observed in other glial cells. It is probable that glycogen accumulation in synaptic terminals of partially deafferentiated Clarke's nucleus may result from impaired glycolysis due to deficient resupply of the distal axon with glycolytic enzymes caused by a defect in axoplasmic transport from the hypoplastic sensory neuronal perikarya.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 75 (1987), S. 41-45 
    ISSN: 1432-0533
    Keywords: Cerebellar hypoplasia ; Critical period ; Hyperbilirubinemia ; Purkinje cell ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The critical period of Purkinje cell degeneration and cerebellar hypoplasia due to bilirubin was examined in rats with transient hyperbilirubinemia induced by a serial subcutaneous injection of novobiocin from 1 to 3, 5 to 7, 10 to 13, or 16 to 20 days after birth. Animals showing total plasma bilirubin levels of 5 to 7 mg/100 ml 6 h after the final injection were used for this study. In nearly midsagittal sections of the culmen, the percentage of the affected Purkinje cells was 0.9%, 17.1%, 0% and 0% at days 3, 7, 13 and 20, respectively. Thus, the Purkinje cells were most vulnerable to bilirubin between days 5 and 7. Cerebella from the rats which showed transient hyperbilirubinemia at day 3, 7, 13 or 20 were weighed at day 30. The cerebellar weight was significantly low only in rats showing hyperbilirubinemia at day 7. Thus, the critical period of the cerebellar hypoplasia due to bilirubin coincided with the period when the Purkinje cells were most sensitive to bilirubin. These results suggest that the Purkinje cell damage leads to the cerebellar hypoplasia in hyperbilirubinemia.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 75 (1987), S. 116-122 
    ISSN: 1432-0533
    Keywords: Rat ; Lead ; Brain edema ; Electron microscopy ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Newborn rats were exposed to daily intraperitoneal injections of 10 mg lead nitrate per kg body weight for the first 15 postnatal days. The growth and mortality of the lead-exposed animals did not differ from their control litter-mates, injected with vehicle only. In our previous studies, focal hemorrhages and spongy areas as well as breakdown of blood-brain barrier to plasma proteins were shown by light microscopy in the cerebellar parenchyma of 15-day-old rats exposed to this dose. In spite of these signs of edema, measurements of brain tissue specific gravity did not show increased water content. In the present investigation we examined the ultrastructure of the brain lesions in these rats with low-dose lead encephalopathy, focusing on signs of edema, and evaluated astroglial reaction by immunocytochemical staining for glial fibrillary acidic protein (GFAP). The electron microscopic findings were compatible with extracellular edema in the cerebellum of 15-day-old lead exposed rats. The number of GFAP-positive cell bodies in the gray substance of the cerebellar cortex was increased in the 15-day-old lead-exposed rats as compared with the controls of the same age, a finding which is presumably related to the leakage of plasma proteins. Both these findings were lacking at 20 days of age, suggesting reversibility of the lead-induced changes.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 24 (1987), S. 260-271 
    ISSN: 1432-1432
    Keywords: Mouse ; Rat ; Two-dimensional electrophoresis ; Quantitative variability of proteins ; Qualitative variability of proteins ; Protein classes ; Membrane proteins ; Organ-specific proteins ; Regulatory genes ; Speciation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Proteins of membranes and cytosols were extracted from the livers and brains of mice (inbred strain DBA/6J) and rats (inbred strain DA/Han) and separated by two-dimensional electrophoresis (2-DE). The 2-DE patterns were compared with regard to qualitative (spot position) and quantitative (spot intensity) characteristics of the proteins of these two species. The following results were obtained: (1) Brain had more (higher percentage) conservative proteins (proteins found in both mice and rats) than liver; (2) plasma membranes had more conservative proteins than the cytosols; (3) organ-unspecific proteins contained more conservative proteins than relatively organ-specific proteins; (4) the pattern of distribution of genetic variability among different classes of proteins represented by findings 1–3 was the same for the qualitative and quantative characteristics of the proteins; and (5) some observations indicated that quantitative variability occurred more frequently among proteins than did qualitative variability. Our conclusion is that regulatory sequences in the DNA (regulatory genes) are subjected to functional constraints that differ in strength among different classes of proteins by the same ratios as the constraints acting on the structural genes. The overall effect of the selective pressure is, however, less stringent for regulatory genes than for structural genes. The results obtained here by comparing two different species are very similar to previous results we obtained by studying different subspecies (inbred strains of the mouse). From this finding arises a new concept: the study of molecular evolution on the basis of different classes of proteins. Our results were compared with data from the literature that were obtained in part from studies on cultured cells. The comparison suggested that cultured cells have lost their tissue-specific proteins, and so generate predominantly extremely conservative proteins.
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  • 10
    ISSN: 1432-0738
    Keywords: Drug-metabolizing enzymes ; Liver ; Rat ; Hepatocarcinogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression, inducibility, and regulation of four different cytochrome (cyt.) P-450 isoenzymes (PB1, PB2, MC1, and MC2) NADPH-cytochrome P-450 reductase, the glutathione transferases (GSTs) B and C and microsomal epoxide hydrolase (mEHb) have been studied during nitrosamine-induced hepatocarcinogenesis using immunohistochemical techniques. The investigations revealed basic differences in the expression of the individual drug metabolizing enzymes in the course of neoplastic development. While the two GSTs and mEHb were increased in all preneoplastic and benign neoplastic lesions, the levels of the distinct cyt. P-450 isoenzymes were characteristically different from each other. Following initial changes in the expression of these enzymes in early preneoplastic lesions (i. e., increase of cyt. P-450 PB1 versus slight decrease of the other cyt. P-450 isoenzymes), a continuous reduction of all cyt. P-450 isoenzymes was observed during the further course of hepatocarcinogenesis. In progressed neoplastic nodules, all cyt. P-450-isoenzymes and NADPH cyt. P-450 reductase were decreased to varying extents. Treatment of animals with inducers of the monooxygenase system, such as phenobarbital, 3-methylcholanthrene and polychlorinated biphenyls, led to a rather heterogenous pattern of enzyme alterations in preneoplastic and neoplastic lesions. Following administration of phenobarbital, some islets responded to the same degree as the surrounding tissue, others were less or not at all inducible and a few of the lesions showed a prominent increase in cyt. P-450 PB2 and NADPH-cyt. P-450 reductase levels. The interesting finding that these two enzymes always showed concurrent changes may be indicative of a common regulation. Similar to phenobarbital, an induction of cyt. P-450 isoenzymes within carcinogen-induced lesions was also observed following administration of 3-methyl-cholanthrene or polychlorinated biphenyls. The results demonstrate that drug-metabolizing enzymes are abnormally regulated in carcinogen-induced lesions. The multiplicity of enzyme deviations within individual lesions and especially the enzyme inducibility strongly suggest that the focal enzyme alterations result from genotoxic effects of the carcinogen on regulatory systems of a higher order rather than from mutational events in individual structural genes.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 59 (1987), S. 328-331 
    ISSN: 1432-0738
    Keywords: Aristolochic acid ; Toxicology ; Acute toxicity ; Rat ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The acute toxic effects of aristolochic acid (AA) were tested in rats and mice of both sexes. Oral or intravenous administration in high doses was followed by death from acute renal failure within 15 days. Histologically, the predominant features were severe necrosis affecting the renal tubules, atrophy of the lymphatic organs and large areas of superficial ulceration in the forestomach, followed by hyperplasia and hyperkeratosis of the squamous epithelium. The LD50 ranged from 56 to 203 mg/kg orally or 38 to 83 mg/kg intravenously, depending on species and sex.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 59 (1987), S. 341-345 
    ISSN: 1432-0738
    Keywords: Rat ; Lead ; Brain ; Myelin basic protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Postnatal exposure of rats to lead has been shown previously to cause CNS hypo-myelination. Since rats intoxicated with lead often show retarded growth, the superimposed malnutrition, which as such can cause hypomyelination, may contribute to myelin deficit. In the present study control rats and lead exposed rats which did not have any retardation of growth were examined by radioimmunological assay of myelin basic protein (MBP) of homogenates of cerebrum and cerebellum at 30, 60 and 120 days of age. Lead was administered on postnatal days 1–15 by daily intraperitoneal injections of 10 mg lead nitrate/kg body weight. This lead dose results in light microscopically discernible hemorrhagic encephalopathy in the cerebellum of 15-day old rats, but does not induce growth retardation (Sundström et al. 1983). The controls were injected with vehicle only. The amount of lead in the blood and brain homogenates of lead-exposed and control rats 15–200 days old was estimated by atomic absorption spectrophotometry. Significant differences between the lead-exposed and control rats were not found in the cerebral or cerebellar content of MBP. Considering the results of previous investigations, the findings do not exclude a hypo-myelinating effect of lead, but they suggest that exposure to lead without concomitant malnutrition does not cause hypo-myelination in the cerebrum and cerebellum of the developing rat.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 61 (1987), S. 21-26 
    ISSN: 1432-0738
    Keywords: m-Xylene inhalation ; Xenobiotic enzymes ; Lung effects and morphology ; Blood concentrations ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were exposed to 0, 75, 150 or 300 ppm (1 ppm=1 cm3/m3=4.35 mg/m3) m-xylene for 24 h and then killed. In the lungs, the cytochrome P-450 decreased to 45, 13 and 20% of the control value with the increasing exposure intensity and the activity of 7-ethoxycoumarin O-deethylase to 70, 27 and 14%, respectively. The activity of epoxide hydrolase increased slightly after exposures both at 150 (1.6-fold) and 300 cm3/m3 (1.4-fold), while the other measured drug-metabolizing enzyme activities showed no consistent changes. The non-protein sulfhydryl group content of the lungs was not affected. The concentrations of m-xylene in blood indicated that the solvent uptake increased in the different exposure groups more than expected, based on atmospheric concentrations alone. Morphologic studies of the lungs with scanning electron microscopy showed no apparent changes after exposure to 300 cm3/m3 or after a high oral dose (2 ml/kg/day, 3 days). Inhalation exposure to m-xylene for 5 weeks (7 h/day, 4 days/week) at a concentration of 300 ppm lowered the contents of cytochrome P-450 in rat lungs to 65% and the activity of 7-ethoxycoumarin O-deethylase to 41% without any other marked effects on the other drug-metabolizing enzymes or on the levels of non-protein sulfhydryl groups. In this study, the selective destruction of cytochrome P-450 in rat lung could be shown both after acute and subacute exposures and at concentrations low enough to warrant occupational concern.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 60 (1987), S. 319-324 
    ISSN: 1432-0738
    Keywords: Bromofenofos ; Organophosphorus anthelmintic ; Embryolethality ; Teratogenicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bromofenofos, an organophosphorus anthelmintic, was administered by gavage to rats as a single dose (50 mg/kg) on one of days 6 through 14 of pregnancy. The dams were killed on day 21, and the fetuses were removed, weighed and examined by routine teratological methods. A significant increase in fetal resorptions occurred after administration on days 9 through 13, with a maximum on day 10. Approximately 72% of the implants were resorbed after administration on day 10. Fetal body weights were significantly decreased when dams were treated on day 8 or later. The greatest decrease in fetal body weights was observed on day 10, when the fetuses weighed less than the controls by about 44% on the average. The incidence of fetuses with gross, skeletal and internal malformations was significantly increased on days 8 through 10, on days 8 through 11 and on days 8 and 9, respectively. Although various types of malformations were observed, most of them occurred on day 8, when no significant increase in fetal resorptions did occur. Cleft lip, short tail, brachygnathia, anal atresia, absence of genital tubercle, fused pelvic legs and perineal testicles were seen on day 8 as gross malformations. Skeletal malformations mainly affected the vertebrae and ribs. Major internal malformations on day 8 were hydronephrosis, hydroureter, anophthalmia, cleft palate, agenesis of the bladder and renal agenesis. Anophthalmia and/or microphthalmia were observed on days 8 through 10, with the highest incidence on day 9. To further determine the no-effect levels for embryolethal and teratogenic effects, a single dose of 10, 20, 30 or 40 mg/kg was administered by gavage to rats on days 8 or 10 of pregnancy. The no-effect levels of single oral dose for embryolethal and teratogenic effects were considered to be 40 and 30 mg/kg, respectively.
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  • 15
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    Electronic Resource
    Springer
    Archives of toxicology 60 (1987), S. 325-327 
    ISSN: 1432-0738
    Keywords: Bromofenofos ; Dephosphate bromofenofos ; Embryolethality ; Teratogenicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bromofenofos (BF) and dephosphate bromofenofos (DBF) were administered at equimolar doses to rats on day 10 of pregnancy. The dams were killed on day 21, and the fetuses were removed, weighed and examined by routine teratological methods. BF caused a significant increase in fetal resorptions at 58.2 mg/kg. Approximately 69% of the implants were resorbed at this dose level. In rats given DBF equimolar to 58.2 mg/kg BF, the resorption rate was 81.9%. Administration of BF resulted in a dose-dependent decrease in fetal body weights which was significant at 29.1 mg/kg or more. DBF caused a significant decrease in fetal body weights, beginning at 25.1 mg/ kg equimolar to 29.1 mg/kg BF, and the decreased fetal body weights were almost the same between BF and DBF. BF at 58.2 mg/kg induced significant gross and skeletal malformations, with incidences of 35.6 and 27.6%, respectively. In rats given DBF equimolar to 58.2 mg/kg BF, gross and skeletal malformations were seen in 54.5 and 61.5% of the fetuses, respectively. There were similarities in the types of malformations observed between BF and DBF. Both compounds induced no significant internal malformations. It was concluded from these results that the embryolethal and teratogenic effects of BF is due to its metabolite, DBF, which cannot respond to cholinesterase inhibition.
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  • 16
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    Electronic Resource
    Springer
    Experimental brain research 65 (1987), S. 465-470 
    ISSN: 1432-1106
    Keywords: Superior colliculus ; Lesion ; Visual search ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The superior colliculus was removed from rats at either one or five days of age or in maturity. Four months later they were tested on two versions of a visual search task. Experiment 1 required animals to retrieve food pellets concealed in a depression in the top of identical narrow pillars arranged in an arena. Rats with lesions of the superior colliculus, regardless of the age at operation, showed a large number of ‘return’ errors compared with sham-operated controls. Return errors were defined as occasions on which the animal returned to pillars that had previously been visited on that trial, before every pillar had been visited at least once. Experiment 2 compared the ability of infantand adult-operated animals to detect and locate a single, baited white pillar in an array of black ones. There were no group differences in response latencies to targets presented in the rostral visual field (within 40° of the midline). However, animals operated on in adulthood or at 5 days of age were slower than both sham-operated animals and animals operated on at one day of age in their responses to more peripheral targets. The latter two groups were indistinguishable.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 65 (1987), S. 513-519 
    ISSN: 1432-1106
    Keywords: Pressure ; Helium ; Rat ; Hippocampus ; CA1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary High pressures of helium affect the physiology of the central nervous system in animals and humans. We examined these effects in rat hippocampal slices. The in vitro preparation displayed a reversible reduction in postsynaptic and antidromic field potentials of CA1 pyramidal cells, but no significant change in the amplitude of the afferent volley. Although the subliminal synaptic response of CA1 neurons was depressed, the ability of these cells to produce population spikes was enhanced. These changes resembled those previously found in vivo in the rat hippocampus. The present results support the hypothesis of a helium pressure-induced depolarization of hippocampal neurons. Other possible mechanisms are discussed.
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  • 18
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    Electronic Resource
    Springer
    Experimental brain research 65 (1987), S. 623-628 
    ISSN: 1432-1106
    Keywords: Olfactory bulb ; Rat ; Tracheotomy ; Centrifugal systems ; Respiratory modulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In behaving rats, unit activity in the mitral and granule cell layers of the olfactory bulb (OB) can be modulated by respiration. In order to determine whether central influences could take part in this phenomenon, respiratory rhythm and the activity of OB units were recorded in the present experiment and analyzed temporally in 18 anaesthetized tracheotomized rats. In spite of the interrupted nasal airflow, 30 of the 80 cells recorded in the mitral and granule cell layers, still displayed a significant respiratory patterning of their activity. Maximal neuronal discharges were time-locked with different phases of the respiratory cycle, most often synchronized with the end of expiration. This is in contrast with previous observations in intact animals. Possible underlying mechanisms are discussed.
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  • 19
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    Electronic Resource
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    Experimental brain research 67 (1987), S. 510-522 
    ISSN: 1432-1106
    Keywords: Rat ; Somatosensory cortex ; Somesthesy ; Proprioception ; Convergence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The foreleg proprioceptive and cutaneous representations, in the Sm cortex of urethane-anesthetized rats was studied. Natural or electrical stimulations and stretches of single forearm muscles were used. Multiunitary, unitary or intra-cellular recordings were performed in the contra-lateral Sm cortex. The aims of the study were: 1 — to compare the proprioceptive and cutaneous maps 2 — to analyse the characteristics of the unitary responses and 3 — to study the laminar distribution of cutaneous and muscular inputs. It is shown that: 1 — the proprioceptive and cutaneous representations overlapped, except in the anterior part where only proprioceptive (mainly articular) responses were obtained. The representation of each stretched muscle extended over the whole cutaneous area, showing a total overlap between inputs from these muscles. 2–46% of the intracellularly recorded cells (n=215) responded to peripheral stimulation, and 30.7% were influenced by (at least) muscle stretch. The majority of excited cells showed cross-modal covergence, and among neurons responding to muscle stretch, 60% received inputs from the two muscles stretched. Two categories of EPSPs were found, and four neurons responded to cutaneous or muscular stimulation with a burst. 19% of the responding cells were inhibited by peripheral — mainly cutaneous — stimulations. 3 —Excited neurons were recorded in all layers, with just over half located in layer IV, whereas IPSPs were obtained mainly in layer V. The cells excited by cutaneous and muscular inputs (convergent neurons) were preponderant in layers IV to VI. This work shows that the cutaneous and muscular inputs reach the same area in Sm cortex, and that a majority of excited cells are “convergent”. The results are not in favor of an area 3a (by analogy with cats and monkeys) in the rat.
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  • 20
    ISSN: 1432-1106
    Keywords: Oculomotor complex ; Superior colliculus ; Pontine reticular formation ; Cerebellar nuclei ; Medial cerebellar (fastigial) nucleus ; Fluorescent tracers ; Rat ; Eye movement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Collateralization of cerebellar efferent projections to the oculomotor region, superior colliculus (SC), and medial pontine reticular formation (mPRF) was studied in rats using fluorescent tracer substances. In one group, True Blue (TB) was injected into the oculomotor complex (OMC), including certain paraoculomotor nuclei and supraoculomotor ventral periaqueductal gray (PAG), and Diamidino Yellow (DY) was injected into the medial pontine reticular formation (mPRF) or pontine raphe. The largest number of single-TB-labeled (paraoculomotor-projecting) cells was observed in the medial cerebellar nucleus (MCN) and posterior interposed nucleus (PIN), whereas the largest number of single-DY-labeled (mPRF-projecting) cells was in the MCN. Double-TB/DY-labeled cells were present in the caudal two-thirds of the MCN, suggesting that some MCN neurons send divergent axon collaterals to the paraoculomotor region and mPRF. In another group, TB was injected into the SC and DY into the mPRF. The largest number of single-TB-labeled (SC-projecting) cells was in the PIN, although a considerable number of cells was observed in the caudal MCN, and ventral lateral cerebellar nucleus (LCN). Single-DY-labeled (mPRF-projecting) neurons were primarily located in the central and ventral MCN, but were also present in the lateral anterior interposed (AIN) and in the LCN. Double-TB/DY-labeled neurons were observed in the caudal two-thirds of the MCN and in the central portion of the LCN. The most significant new findings of the study concerned the MCN, which not only contained neurons that projected independently to the paraoculomotor region, SC, and mPRF, but also contained a considerable number of cells which collateralized to project to more than one of these nuclei. The possibility that the MCN projects to the supraoculomotor ventral PAG (containing an oculomotor interneuron system) and to the mPRF, which in the cat and monkey contain neural elements essential to the production of saccadic eye movements, is discussed. The anatomical findings suggest that the MCN in the rat plays an important role in eye movement.
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  • 21
    ISSN: 1432-1106
    Keywords: Prefrontal cortex ; Ammon's horn ; CA1 ; WGA-HRP ; Antidromic stimulation method ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Following microinjection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the medial prefrontal cortex (defined as the neocortical area innervated by the thalamic mediodorsal nucleus) labelled cells were observed in the pyramidal layer of the CA1 field of Ammon's horn. Observations made using antidromic stimulation confirmed these results, and revealed the slow conduction velocity of the fibres of the hippocampal cells innervating the prefrontal cortex. Taken together, these data provide evidence for a direct projection of CA1 cells to the medial prefrontal cortex.
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  • 22
    ISSN: 1432-1106
    Keywords: Vasopressin neurons ; Monoclonal antibodies ; Gyrus dentatus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The fate of monoclonal anti-vasopressin antibodies (VP-MAbs) injected in vivo into the paraventricular nucleus (PVN) of the rat brain was studied by immunocytochemistry. Depending on the post survival time, VP-MAbs contained in an ascites fluid were stained at different levels of the VP neurons: the cytoplasm of the PVN neurons, the fibres of the median eminence and the granular layer of the Gyrus Dentatus. The identification of endogenous peptides synthesized by PVN neurons showed that the VP-MAbs uptake was specific: it did not appear either in the oxytocinergic neurons or in the non immunoreactive neurons of the Brattleboro rat brain, this rat being genetically incapable of synthesizing central VP. Conversely, VP-MAbs only penetrated into the VP neurons: ascites fluid containing monoclonal antibodies prepared against bovine thyroglobulin (the carrier conjugated to VP in our immunizations) was neither stained in magnocellular neurons nor carried in nerve fibres. The neuronal uptake and transport of VP-MAbs occurred in vivo: they were totally inhibited by heating of the ascites fluid at 56° C for 30 min; this treatment did not alter the VP-MAbs themselves but probably destroyed some thermic sensitive component essential to the macromolecule internalization. The biological effects of antibodies injected in vivo have been reported. The results described here suggest that some specific antibodies passively transferred into the brain could act directly on the peptide synthesis recognized by the antibodies.
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  • 23
    ISSN: 1432-1106
    Keywords: Carrageenin hyperalgesia ; Rat ; Ventro-basal thalamic neurones ; Responses to mechanical stimuli
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neuronal response thresholds and the encoding of mechanical stimulus intensity in the ventro-basal (VB) thalamus was analyzed in anaesthetized rats before and during the first two hours following induction of hyperalgesic inflammation. This inflammation was induced by the intra-plantar injection of carrageenin in the hindpaw contralateral to the recorded neurones. Only neurones exclusively driven by noxious stimuli and with a receptiv field on or including the injected paw were considered. In this early phase of the inflammatory process, there was no significant modification of the response threshold to the mechanical stimulus (indentation of about 300μm). This suggests the involvement of additional neuronal population(s) to account for the decrease in the vocalisation threshold to pressure observed in the freely moving animal at this time of the inflammation, A liner encoding of the indentation depth was observed before and after the carrageenin injection although the slope of the stimulus response-curve was steeper after the injection. The data emphasize that the carrageenin-sensitization acts differentially on the liminal and supra-liminal responses of the same neurone to a skin indentation, since in the first hour following the initiation of the inflammation the sensitization is essentially observed for responses obtained with stimulus intensity largely above the threshold value. With regard to previous observations using thermal stimulation, the results also illustrate that the carrageenin induced sensitization of responses differs depending on the stimulus intensity and modality used.
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  • 24
    ISSN: 1432-1106
    Keywords: Medial precentral cortex ; Anterior cingulate cortex ; Frontal eye field ; Superior colliculus ; Oculomotor complex ; Paraoculomotor nuclei ; Medial pontine reticular formation ; Eye movement ; Rat ; Fluorescent tracers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Paired injections of fluorescent tracers (True Blue, Diamidino-Yellow) were made into the oculomotor complex (OMC) and medial pontine reticular formation (mPRF), and superior colliculus (SC) and mPRF, in adult rats to retrogradely label the cortical cells of origin of projections to these oculomotor-related brainstem structures. While large numbers of single-labeled cells in the medial frontal cortex projected only to the mPRF, the presence of many double-labeled cells in the dorsomedial shoulder cortex (medial precentral/anterior cingulate areas), the rat frontal eye field (FEF), indicated that this cortical region contains lamina V pyramid neurons whose axons collateralize to project to the region of the OMC, SC, and mPRF. The similarities of rat and monkey FEF connections, and their relevance to the control of eye movement, are discussed.
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  • 25
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    Experimental brain research 65 (1987), S. 261-270 
    ISSN: 1432-1106
    Keywords: Acetylcholine ; Efferent cochlear systems ; Choline acetyltransferase ; Immunoelectron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using anatomical criteria, the olivo-cochlear fibers ending in the organ of Corti (efferent fibers) have recently been separated into two systems: a lateral system innervating principally the inner hair cell (IHC) area and a medial system innervating mainly the outer hair cells (OHCs). Electrophysiological and biochemical experiments suggest that acetylcholine may be a neurotransmitter of these efferent fibers. However, efferent synapses that use acetylcholine as neurotransmitter have not yet been identified at the electron microscopic level. Using a pre-embedding immunoelectron microscopic technique with a monoclonal antibody against choline acetyltransferase (ChAT), we localized ChAT-immunostained fibers below both the IHCs and OHCs. In the inner spiral bundle, one type of ChAT-immunostained fibers was vesiculated and formed axo-dendritic synapses with the afferent auditory dendrites contacting the inner hair cells. A second type of ChAT-immunostained fibers seen in the inner spiral bundle was unvesiculated. Unstained vesiculated varicosities synapsing with the auditory dendrites were also seen in the inner spiral bundle. At the OHC level, ChAT immunostaining was found in nearly all the terminals synapsing with the OHCs. The finding of two types of ChAT-immunostained efferent synapses in the organ of Corti, i.e. axodendritic synapses in the inner spiral bundle and axosomatic synapses with the OHCs, supports the hypothesis that both the lateral and the medial olivocochlear systems use acetylcholine as a neurotransmitter. The finding of numerous unstained synapses in the inner spiral bundle, and some below OHCs, together with previous data about putative cochlear neurotransmitters, suggests the possibility of additional non-cholinergic olivo-cochlear systems. It might soon appear useful to reclassify efferents according to the nature of the different neurotrans-mitters/ co-transmitters found in the various efferent synapses of the organ of Corti.
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  • 26
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    Experimental brain research 65 (1987), S. 449-454 
    ISSN: 1432-1106
    Keywords: Substantia nigra ; Brain tissue transplantation ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous experiments have proven brain tissue transplantation effective in reversing lesioninduced behavioral deficits in mature rats. This study reversed the usual experimental paradigm, so that fetal substantia nigra was transplanted into intact neonatal rats and allowed to mature in the host brain. Upon maturation substantia nigra lesions were made bilaterally to reveal the functional contribution of the transplanted tissue. In control animals these lesions depleted striatal dopamine, producing rigidity, poverty of movement and abnormal posture comparable to Parkinson's disease in the human; cessation of feeding and drinking led to progressive weight loss and death. In contrast, fetal substantia nigra transplanted into the neonatal rat became well-integrated in the host brain and was shown to protect the animal from this syndrome produced by subsequent substantia nigra lesions. We suggest that transplantation in these neonatal rats was performed during a crucial period of synaptogenesis, an environment particularly favorable to host-transplant interaction.
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  • 27
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    Experimental brain research 66 (1987), S. 74-82 
    ISSN: 1432-1106
    Keywords: Preoptic area ; Suprachiasmatic nucleus ; Morphometry ; Rat ; Streptozotocin diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pituitary and gonadal disorders consistent with abnormal LHRH and LH secretion occur in streptozotocin-diabetic rats. A key role in the synthesis and regulation of LHRH and in the phasic LH release is played by the preoptic-suprachiasmatic region which is mainly formed by the medial preoptic area, the sexually dimorphic nucleus of the medial preoptic area, and the suprachiasmatic nucleus. Therefore we have studied this region by morphology and morphometry in normal and streptozotocindiabetic rats. In normal animals, the neurons of the above mentioned nuclei were morphologically and morphometrically dissimilar. Independent of their localization, reduced cytoplasmic and nuclear areas were observed in the neurons of diabetic animals. These lesions are consistent with hypotrophied neurons. Consequently, diabetes may impair both synthesis and regulation of LHRH and may therefore account for pituitary disorders, testicular atrophy, and lacking preovulatory LH peaks. The structural differences of the neurons of the three nuclei in normal animals underline their different physiological role. Yet, the similarity of the changes found in all three nuclei suggests a generalized hypofunction of the whole preoptic-suprachiasmatic region under diabetic condition.
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  • 28
    ISSN: 1432-1106
    Keywords: 3-acetylpyridine ; Climbing fiber ; Inferior olive ; Vestibulospinal tract ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The inhibitory action of Purkinje cells on vestibulospinal tract (VST) cells was examined in rats deprived of climbing fibers with 3-acetylpyridine (3-AP) intoxication. In order to resolve discrepancies raised in previous studies with various means, special efforts were devoted to directly estimate Purkinje cell inhibition at synaptic levels by using intracellular recording, to avoid sampling bias by using a systematic survey of VST cells in each rat, and to evaluate the time-dependence of the effects of climbing fiber deafferentation by regular testing at 10 day intervals until 160 days after 3-AP intoxication. As compared with 661 VST cells impaled in 15 control rats, 1771 VST neurons impaled in 29 3-AP-treated rats revealed four basic changes in the monosynaptic inhibitory postsynaptic potentials (IPSPs) induced by stimulation of Purkinje cell axons in the white matter of the cerebellar anterior lobe. First, the rate of IPSP occurrence among VST cells was 0.64 in control rats; at more than 10 days after 3-AP intoxication it decreased gradually, down to 0.37–0.38 at the 70th–81st days, and thereafter increased up to 0.53 by the 160th day. The rate of IPSP occurrence varied considerably between the rostral and caudal regions, and also between the dorsal and ventral divisions of the VST cell population, but its reduction after 3-AP intoxication occurred approximately in parallel in all divisions. Second, IPSPs evoked with standard 500 μA pulse stimuli were smaller in size on and after day 10. The reduction of IPSP size was by as much as 53% of control values at the 70th–101st days in the dorsal division, but no significant change occurred in the ventral division of the VST cell population. Third, the latency of the IPSPs was prolonged by about 0.25 ms on and after day 10. Analysis of the relationship between the IPSP latency and the dorsoventral location of VST cells in the medulla suggests that the major cause for the prolongation of IPSP latency is an increased synaptic delay at Purkinje cell axon terminals. Fourth, the cerebellar stimulation threshold for evoking IPSPs was almost always below 100 μA in control rats, but values of 100–250 μA were common after the 40th day. Thus, climbing fiber deafferentation exerts long-term influences on excitability of Purkinje cell axons, and on the connectivity and synaptic transmission from Purkinje cell axons to VST cells.
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  • 29
    ISSN: 1432-1106
    Keywords: Amino acids ; Immunocytochemistry ; Specificity testing ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Specificity testing should be performed under conditions identical to or closely similar to those of the immunocytochemical procedure. This paper describes a new model system that meets this requirement for postembedding immunocytochemistry of amino acids at the light- and electron microscopic levels. Test conjugates, obtained by reacting different amino acids with brain macromolecules in the presence of glutaraldehyde, were freeze-dried and embedded in an epoxy resin (Durcupan) exactly as for brain tissue. One section from each of the embedded amino acid conjugates and from a brain protein-glutaraldehyde conjugate (without amino acid) were piled on top of each other and embedded anew. Transverse semithin (0.5 μm) and ultrathin sections were cut through the stack. These test sections, in which all the different conjugates were represented, were then processed in the same drops of sera as the tissue sections to permit identical conditions for testing and immunocytochemistry. After immunogold labelling for electron microscopy, a quantitative expression of crossreactivity was obtained by computer-assisted calculation of gold particle densities over the different conjugates. The antisera used in the present study (glutamate anti-serum 13, taurine antiserum 20, and GABA antiserum 26) showed highly selective labelling of the respective amino acid conjugates and produced distinct labelling patterns in simultaneously processed cerebellar sections.
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  • 30
    ISSN: 1432-1106
    Keywords: Glutamate-specific antiserum ; Immunocytochemistry ; Primary sensory neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We found that large cells in the dorsal root and trigeminal ganglia contained glutamate-like immunoreactivity. Immunoreactive neurons were not detected in the superior cervical or pterygopalatine ganglia. These findings indicated that glutamate is a neurotransmitter or neuromodulator of large cells of sensory ganglia.
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  • 31
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    Experimental brain research 65 (1987), S. 686-690 
    ISSN: 1432-1106
    Keywords: Brainstem auditory evoked potential ; Low pass filtering ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of low pass filtering on the brainstem auditory evoked potential (BAEP) were studied in the adult male rat. The bandpass of the recording system was progressively widened while the cut-off frequency of the high pass filter remained constant at 3.2 Hz. When the high frequency cut-off was 320 Hz or less, the principal waveform recorded in response to a click stimulus was a slow positive-negative complex. As the high frequency setting was raised from 800 Hz to 3.2 kHz, the slow components of the brainstem were replaced by four fast BAEP waves (I, II, III and IV). As the bandpass widened there was an increase in amplitude and a decrease in the absolute latency of all four fast waves in the order of 0.1 ms although the wave I–IV interpeak latency remained unaffected. The results confirm that the high frequency components of the BAEP are underlain by a slow positivity of uncertain origin followed by a slow negativity which probably arises within the inferior colliculus.
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  • 32
    ISSN: 1432-1106
    Keywords: Glycine ; GABA ; Immunocytochemistry ; Cerebellum ; Golgi cells ; Colocalization ; Rat ; Baboon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An antiserum against conjugated glycine was characterized and applied to cerebellar sections of rats and baboons that had been perfusion-fixed with glutaraldehyde. After immunosorbent purification the serum reacted with brain protein-glutaraldehyde-glycine conjugates, but did not stain similar test conjugates prepared from other amino acids, including GABA and β-alanine. In the rat cerebellum the glycine antiserum selectively labelled a subpopulation of Golgi neurons. Adjacent Vibratome sections treated with an antiserum against conjugated GABA revealed an about equally large subpopulation of immunopositive Golgi cells. A proportion of the Golgi cells that were cleaved by the plane of section contained both immunoreactivities. Additional evidence for a colocalization of glycine and GABA was obtained by postembedding staining of alternate semithin sections with the GABA antiserum and glycine antiserum, respectively. The ability of the antisera to distinguish between fixed glycine and GABA was corroborated by preincubation of the antisera with glutaraldehyde-amino acid fixation complexes: glycine complexes abolished staining with the glycine antiserum but had no effect on the GABA antiserum. The opposite effects were obtained with the GABA complexes. Matching the distributions of the respective immunoreactivities, [3H]glycine uptake was restricted to glomerulus-like structures in the granule cell layer whereas [3H]GABA uptake also occurred in punctate and fibrous profiles in the molecular layer. The baboon showed a distribution of glycine-like immunoreactivity similar to that in the rat, except that a few immunopositive neurons occurred in the molecular layer. The latter neurons were interpreted as outlying Golgi neurons; however, the possibility that they represent a subpopulation of basket cells could not be excluded. The Purkinje cells were negative in both species. Glial cells were weakly stained with the glycine antiserum but were strongly immunopositive after incubation with an antiserum raised against conjugates of the structurally similar amino acid β-alanine. The present data suggest that glycine and GABA occur in about equally large subpopulations of Golgi neurons. A subpopulation of the Golgi neurons appears to contain both glycine and GABA.
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  • 33
    ISSN: 1432-1106
    Keywords: Deprivation ; Rat ; Visual cortex ; Development ; Synapse morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The quantitative effects of dark-rearing and light exposure on the ultrastructural characteristics of synapses and synaptic boutons in layer 4 of the rat visual cortex (area 17) have been investigated using stereological techniques. Two experimental groups (each containing 5 animals) were investigated i) animals dark-reared upto weaning at 21 days post natum (21DPN) and then light exposed until 52DPN (Group 21/31), and ii) littermate animals totally dark-reared until 52DPN (Group 52dD). The results indicate a significantly higher mean density of synapses in the neuropil of layer 4 in group 21/31 (3.58×108 · mm-3) compared with group 52dD (2.68×108 · mm-3). Although the density per unit volume of synapses with identified asymmetrical synaptic membrane specialisations was not significantly different in group 21/31 than in group 52dD (but was significantly lower than animals reared normally), the density of synapses with identified symmetrical synaptic membrane specialisations was about 200% higher in group 21/31 versus group 52dD. However, significant differences were detected in the number of asymmetrical synapses established by single synaptic boutons in group 21/31 (1.21 ± 0.11) compared with group 52dD (1.10 ± 0.09). On the basis of the numbers of post-synaptic targets contacted by an individual synaptic bouton, a significantly higher density of synaptic boutons was found in group 21/31 (2.32×108 · mm-3) compared with group 52dD (1.82×108 · mm-3). Furthermore, planar quantitative data indicated significant inter-group differences in the ultrastructure of asymmetrical and symmetrical synaptic boutons. The results of this study provide evidence indicating marked structural alterations in the synaptic connectivity of layer 4 of the rat visual cortex following the light exposure of rats dark-reared upto weaning. Indeed visual deprivation severely affected the ‘inhibitory’ circuitry in the major thalamorecipient territory of the visual cortex.
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  • 34
    ISSN: 1432-1106
    Keywords: Spike train analysis ; Spontaneous activity ; Primary culture ; Neuronal development ; Occipital cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of spontaneous bioelectric activity (SBA) was studied in dissociated occipital cortex cultures prepared from 19 day old rat fetuses. All cultures, recorded one per diem from 5 to 33 days in vitro (div), showed SBA. Computer analysis of 76 extracellularly recorded single unit spike trains was carried out after selection on the basis of stationarity criteria. Statistically significant developmental trends were found in (i) interspike interval dependencies and (ii) fluctuations in mean firing rate, on the order of a minute or longer. The highly dependent firing patterns, including stereotyped bursting, were present mostly in the 9–12 div group, whereas minute-to-minute fluctuations in the intensity of firing were considerably more pronounced in the oldest group (22–33 div) than in the younger cultures. In addition, firing categories defined on the basis of factor-analysis revealed that such fluctuations were almost exclusively to be found in neurons which fired in a pronounced ‘burst’, rather than a relatively continuous fashion. Only a few mature appearing synaptic structures were observed electron microscopically prior to 12 div, but increased steadily in number thereafter. No cultures prior to 14 div, but all cultures older than this, stained positively for the presence of glutamic acid decarboxylase. An extensive immunoreactive, putative GABAergic, network was present by three weeks in vitro.
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  • 35
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    Experimental brain research 68 (1987), S. 458-465 
    ISSN: 1432-1106
    Keywords: Parabrachio-thalamic relay neurons ; Parabrachial nucleus ; Taste ; Mechanoreception ; Receptive field ; Oral cavity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Receptive fields (RFs) of 36 taste (the 22 parabrachio-thalamic relay (P-T) and 14 non-P-T) and 23 mechanoreceptive neurons (7 P-T and 16 non P-T) were located in the oral cavity of rats. All of the taste and most of the mechanoreceptive units examined had an RF on the ipsilateral side of the tongue or palate, but some mechanoreceptive P-T and non-P-T units had RFs bilaterally. When the RFs of taste neurons were examined with the most effective of the four basic taste (the best stimulus) and non-best stimuli, no difference was noticed in the location of RFs between the P-T and non-P-T neurons. Though most of the P-T neurons (7/11) and all of the non-P-T neurons (6/6) had an RF for non-best stimuli at a region similar to that for the best stimulus, some P-T neurons (4/11) had an RFs for non-best stimulus outside the RF for the best stimulus and/or on the region separate from the RF for the best stimulus. The P-T neurons, responding vigorously to non-optimal stimuli as well as to the best stimulus, had an RF outside the RF for the best stimulus. RFs for mechanical stimulation were also examined in some taste and mechanoreceptive neurons. The mechanoreceptive P-T units rarely had an RF exclusively on the palate. Some mechanoreceptive units had an RF on the region where no taste RF has been found, e.g. the intermolar eminence and the folium of the hard palate.
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  • 36
    ISSN: 1432-2307
    Keywords: Human ; Rat ; Breast ; Mammary
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normal human breast organoids, derived by collagenase digestion of reduction mammaplasty tissue specimens, have been cultured in vitro for up to 28 days after injection into organ cultures of virgin rat mammary fat pads. The culture medium was serum-free Waymouth's MB 752/ 1 with hormonal additives. The rat mammary tissue responded well to growth-promoting and lactogenic stimuli in the culture medium, in agreement with previous investigations. Using immunohistochemistry casein was identified in rat epithelia exposed to lactogenic medium. Human organoids in culture remained viable but did not show hormone-responsiveness. Electron microscopy confirmed the presence of both luminal epithelial cells and myoepithelial cells. The serum-free culture of normal human breast organoids in a three-dimensional matrix provides a system in which to study factors controlling growth and differentiation.
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  • 37
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    Archives of toxicology 59 (1987), S. 443-447 
    ISSN: 1432-0738
    Keywords: Rat ; Cadmium ; Injection route ; Teratogenesis ; Maternal liver damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rats of the present (re-derived) Wistar-Porton strain that are dosed either intravenously (i.v.), or intraperitoneally (i.p.) with Cd (1.25 mg/kg body weight) on day 12 of gestation (gd 12), foetal uptake of Cd is at least 6-fold greater than that reported in an earlier study (Webb and Samarawickrama 1981). Higher doses (1.5 and 2.0 mg/kg body weight) are lethal to the maternal animal when administered i. v., but not if given ip. The foetotoxicity of i.p. injected Cd, however, increases with the dose over the range 1.25–2.0 mg Cd/kg body weight. The teratogenic response, which is also wider than that observed previously, is maximal after the injection of 1.25 mg Cd/kg body weight i.v. on gd 10 and i.p. on gd 12. Whilst the incidences of hydrocephalus, urogenital abnormalities, cleft palate and other less common defects are similar after dosing by both routes, the incidence, range and severity of skeletal malformations are greater after i. p. than after i.v. administration of Cd on gd 12. This difference in response is unlikely to be explained by a difference in either foetal, or placental uptake of the metallic ion since, at 4 h after i.p. dosing, the foetal concentration of Cd is not significantly different from that after i.v. injection, whilst the placental concentration is about 33% less. It is suggested that damage to the maternal liver, which is more severe after the i.v. injection of the optimum dose, may be an additional factor that, in conjunction with the inhibition of transport in the placenta and biosynthetic processes in the embryo/foetus, contributes to the teratogenic effects of Cd in the pregnant rat.
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  • 38
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    Archives of toxicology 60 (1987), S. 394-396 
    ISSN: 1432-0738
    Keywords: Barbiturate poisoning ; Pentobarbitone ; Phenobarbitone ; Gastric emptying ; Gastrointestinal transit ; Peristaltic reflex ; Rat ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anaesthetic doses of pentobarbitone (50 mg/kg) were found to inhibit gastric emptying and gastrointestinal transit in the rat. Gastric emptying was more profoundly suppressed than gastrointestinal transit. Phenobarbitone (150 mg/kg) had a similar effect. Since pentobarbitone and phenobarbitone also blocked the peristaltic reflex in the isolated small intestine of the guinea-pig, it would appear that the inhibitory effect of anaesthetic doses of barbiturates on gastrointestinal motility is mainly due to a direct action on the digestive tract. Together with the observation that considerable amounts of phenobarbitone were found in the stomach of an intoxicated patient 3 days after drug intake, these results might indicate that gastric lavage should also be considered in the treatment of protracted barbiturate poisoning.
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  • 39
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    Archives of toxicology 60 (1987), S. 77-80 
    ISSN: 1432-0738
    Keywords: n-Hexane ; Pharmacokinetics ; Man ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of inhaled n-hexane in rat and man were compared. In the rat metabolism was saturable. Up to 300 ppm, the metabolic rate was directly proportional to the concentration in the atmosphere, reaching 47 μmol/(h· kg). Only 17% of n-hexane was exhaled unchanged. Above 300 ppm, the amount of n-hexane in the body rose with increasing atmospheric concentrations from 1.6 up to a limiting value of 9.6, which corresponded to the thermodynamic distribution coefficient of n-hexane between the organism and the atmosphere. Up to 3000 ppm, the rate of metabolism increased to 245 μmol/ (h· kg); only a slow further increase was found up to 7000 ppm (285μmol/(h· kg)). In man the steady-state concentrations of n-hexane were about 1 ppm. The metabolic clearance was 1321/h, and n-hexane accumulated to a factor of 2.3 in the organism. The thermodynamic distribution coefficient was calculated to be 12. Twenty per cent of n-hexane in the body was exhaled unchanged. At low concentrations the rate of metabolism of n-hexane is limited in both species by transport to the enzyme system. Under these conditions the rate of metabolism of n-hexane should not be influenced by xenobiotics which induce the n-hexane metabolizing enzyme system.
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  • 40
    ISSN: 1433-8580
    Keywords: Zona glomerulosa ; Dopaminergic system ; Aldosterone ; Rat ; Stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of metoclopramide (MTC) and bromocriptine (BRC) (two drugs which act as antagonist and agonist of DOPA-receptors, respectively) on the zona glomerulosa of dexamethasone/ACTH-treated rats were investigated by coupled biochemical and morphometric techniques. Shortterm (1-h) MTC administration significantly increased the plasma concentration of aldosterone, while long-term (7-day) MTC administration, as well as short- and long-term treatment with BRC did not cause any apparent change. Long-term MTC administration was found to significantly potentiate both the rise in the plasma level of aldosterone and the hypertrophy of the zona glomerulosa and its parenchymal cells induced by a prolonged treatment with angiotensin II (AII), but not those evoked by a chronic sodium deprivation alone or combined with AII infusion. Long-term BRC administration notably counteracted the effects of sodium restriction (coupled or not with AII infusion), but not those induced by the administration of AII alone. Long-term MTC administration partially reversed both the lowering of the plasma concentration of aldosterone and the atrophy of the zona glomerulosa and its parenchymal cells caused by a prolonged sodium-loading (combined or not with captopril infusion), but not those produced by the administration of captopril alone. On the other hand, long-term BRC treatment induced a further significant reduction in the blood level of aldosterone and the volume of zona glomerulosa and its cells only in captopriltreated animals. These findings are consistent with the view that the dopaminergic system exerts a maximal tonic inhibitory effect not only on the secretory activity, but also on the growth and steroidogenic capacity of the rat zona glomerulosa. Furthermore, they suggest that the activity of the dopaminergic system is in turn controlled by the sodium balance, being almost completely suppressed by a prolonged sodium deprivation.
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  • 41
    ISSN: 1432-2013
    Keywords: Rat ; Skeletal muscle ; Age ; Catechol-amines ; α-Adrenergic receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of increasing age on contractile performance and catecholamine receptor activity was investigated in a distal, predominantly fast twitch oxidative glycolytic (FOG) muscle from the plantar surface of the rat hindfoot. The ability of the flexor digitorum brevis (FDB), isolated from anesthetized rats and maintained in vitro, to undergo post-tetanic potentiation and a staircase response declined with age. Potentiation following repetitive stimulation was reduced by 50% in 2 year old rats and eliminated in 3 year old animals. The rate of muscle fatigue during intermittent tetanic stimulation also increased in aging muscles. FDB, regardless of age, did not develop a positive inotropic response to 10−6 M epinephrine applied in vitro, but 3 year old FDB generated a prolonged contracture. Contracture tension was approximately 25% of twitch tension and was maintained for 2–10 min in the continued presence of catecholamine. Contractures were eliminated by pretreatment with α-adrenergic antagonists or by removing Ca2+ from the bathing medium. In addition to decreased contractile capacity, aging muscles acquire a population of α-adrenergic receptors which may underlie some of the metabolic and structural changes associated with increasing age.
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  • 42
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    Pflügers Archiv 408 (1987), S. 438-443 
    ISSN: 1432-2013
    Keywords: Tubuloglomerular feedback ; Rat ; Furosemide ; Proximal tubule ; Micropuncture ; Kidney ; Entrainment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies in rat kidneys have demonstrated that oscillations in the proximal intratubular pressure are a prominent feature of the tubulo-glomerular feedback mechanism (TGF) operating during free flow conditions. The purpose of the present study was to investigate whether a subpopulation of synchronized, interacting nephrons could be detected. In group A nephrons, i.e., nephrons with a high probability of having their afferent arterioles arising from the same interlobular artery, 29 out of 33 pairs of nephrons were found to show synchronized pressure oscillations. In group B nephrons, not expected to have this common origin of their afferent arterioles, only 1 out of 23 pairs was found to be synchronized. The standard deviation of the frequency differences was 0.063 cycles per minute in group A nephron pairs and 0.202 cycles per minute in group B pairs (p〈0.05), showing the greater homogeneity in frequency in group A. Furthermore, nephrons having synchronized pressure oscillations were found to interact with each other. Thus, perturbation of the proximal tubular pressure oscillations in one nephron by loop microperfusion affected the amplitude of the pressure oscillations in the non-perfused nephron; and reactivation of pressure oscillations in one nephron was followed by reactivation of oscillations in the non-perfused nephron. Thus, the present results show that there exists a well defined subpopulation of nephrons, in which the TGF-mediated proximal pressure oscillations are synchronized. This synchronization is a result of interaction between the different nephrons. It is suggested that the interaction is a consequence of “cross-talk” between the TGF signals from the different nephrons concerned, transmitted along the afferent arterioles, and probably also along a part of the interlobular artery.
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  • 43
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    Pflügers Archiv 408 (1987), S. 543-551 
    ISSN: 1432-2013
    Keywords: Fibre types ; Fibre transformation ; Enzymes of energy metabolism ; Slow and fast skeletal muscle ; Rat ; Age ; Endurance training
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of age and endurance training on muscle fibre characteristics were studied in a slow (m. soleus, MS) and in a fast (m. rectus femoris, MRF) skeletal muscle. Wistar rats at ages of 1, 2, 4, 10, and 24 months were used as experimental animals. The trained rats were put to run on a motor-driven treadmill 5 d/wk beginning from the age of 1 month. The body weights of the animals increased continuously throughout their lives. The muscle weights increased up to the age of 10 months, after which they tended to decrease. The trained adult rats had lower body weights as well as lower muscle weights than the untrained adult rats. The amount of the intramuscular lipid decreased with age, especially during the first months of life. The activity of isocitrate dehydrogenase (ICDH) decreased during the growth period in both muscles and remained more or less constant thereafter, whereas the activity of phosphofructokinase decreased with age only in MS. In MS, the trained animals tended to have higher ICDH activities than the untrained animals. The cross-sectional area of the different fibre types in both muscles increased up to the age of 10 months. The major fibre types, type I in MS and type IIB in MRF, were smaller for trained than untrained rats. The percentage number of the slower fibre types of both muscles — type I in MS and types I and IIA in MRF —increased with advancing age. The muscles of the trained animals contained higher percentages of the slower fibre types than those of the untrained rats. The present paper indirectly supports the opinion that not only the metabolic but also the contractile properties of different muscle cell types can be changed by age and long-term endurance-type physical training.
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  • 44
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    Pflügers Archiv 409 (1987), S. 492-498 
    ISSN: 1432-2013
    Keywords: Rat ; Micropuncture ; Sodium ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Micropuncture and clearance studies were performed on rats with chronic metabolic acidosis to evaluate the segmental handling of magnesium. Fractional magnesium excretion was 12.6±2.3% in acidemic rats (blood pH 7.17+0.2) compared to 5.1±1.3% of normal animals (blood pH 7.36±0.05). Ultrafilterable magnesium concentrations were similar in both normal and acidotic animals, 0.51±0.02 and 0.48±0.03 mM, respectively. Elevation of urinary magnesium excretion was due to diminished reabsorption in the loop of Henle and segments beyond the distal sampling site. Acute correction of the systemic acidosis with NaHCO3 infusions partially corrected the renal magnesium levels as fractional magnesium excretion fell from 12.6% to 3.1+0.75%. This was associated with enhanced reabsorption of magnesium in the loop. To determine if acidosis may compromise the renal conservation of magnesium, acidotic rats were subsequently placed on magnesium-restricted diets. Normal and acidotic animals adapted appropriately and to a similar extent when challenged by short-term magnesium-restricted diets. Accordingly, elevation of dietary acid intake and systemic acidosis leads to renal magnesium wasting which is due in part to diminished reabsorption in the loop of Henle. However, chronic acidosis does not compromise the renal adaptive response to dietary magnesium restriction.
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  • 45
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    Pflügers Archiv 409 (1987), S. 220-222 
    ISSN: 1432-2013
    Keywords: Rat ; isolated perfused kidney ; isolated perfused liver ; combination of
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interaction between hepatic and renal metabolism is found in many endocrine systems. We therefore developed a new experimental model, combining the isolated perfused rat kidney and rat liver. Krebs-Henseleit buffer with bovine serum albumin 67 g·1−1 and amino acids was recirculated to both organs through two rolling pumps, four 8 μm Millipore filters and two specially designed membrane lungs. The kidney was cannulated by a modification of the technique described by Nishiitsutsuji-Uwo 1967 and the liver was cannulated by a modification of the technique described by Hems 1966. Kidney function: Perfusion pressure 12.4±1.1 kPa (93±8 mmHg), flow 28±6 ml·min−1·g−1, FRNa 94.0±2.9%, GFR 491±191 μl·min−1·g−1, urine production 48±34 μl·min−1·g−1, FEK 60±36%. Liver function: Flow 25 ml·min−1 (fixed), portal vein pressure 12±3 cm H2O, bile flow 0.18±0.13 ml·h−1, oxygen consumption 2.0±0.2 μmol·min−1·g−1. Only minor differences were found between single perfusions (N=25) and combined perfusions (N=6). We conclude that it is possible to combine the isolated perfused rat kidney and rat liver without impairment of the function of either.
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  • 46
    ISSN: 1432-2072
    Keywords: Apomorphine ; Conditioned dopaminergic activity ; Stereotyped behaviour ; Dopamine autoreceptors ; Dopamine metabolism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated whether pharmacological effects of the dopamine agonist apomorphine can be conditioned by establishing an association of apomorphine administration with exteroceptive cues. Apomorphine was repeatedly administered and subsequently, the rat was put into a test cage and exposed to an acoustic and an olfactory stimulus (“conditioned rats”). Control animals (“pseudoconditioned” rats) were treated with the same pharmacological schedule of apomorphine not temporally associated with the stimuli. On the test day, both groups were injected with saline and exposed to the stimuli described. The stereotyped behaviour produced by large doses of apomorphine (0.5 or 2.0 mg/kg SC), namely sniffing, licking and gnawing, could be conditioned in a pronounced way. During the conditioning period, a change in the stereotypies was observed with regard to the time-course (earlier occurrence) and to the character of the stereotypies (from sniffing to licking and gnawing), when 0.5 mg/kg apomorphine was used, but not with the dose of 2.0 mg/kg. The conditioned responses showed a relatively uniform distribution during the observation period with some increase towards the end of the observation period. Some signs produced by a low dose of apomorphine (0.07 mg/kg SC), namely hypomotility and ptosis, but not yawning, could also be conditioned, although in a less pronounced way. An intermediate dose of apomorphine (0.18 mg/kg SC) produced both signs observed after large doses and those observed after a small dose, occurring alternatingly. Both types of signs could be conditioned using this dosage. Conditioning did not alter striatal or mesolimbic dopamine turnover. These results suggest that only behavioural signs due to an activation of postsynaptic dopamine receptors, but also some symptoms produced by an activation of dopamine autoreceptors can be conditioned.
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  • 47
    ISSN: 1432-2072
    Keywords: Pituitary-adrenal function ; Behavioral despair ; Clomipramine ; Anti-depressant ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interaction between the effects of chronic electrical tail shock and clomipramine (CMI) on exploratory activity, behavioral despair and pituitary-adrenal function was studied in adult male rats. Both CMI and shock administered alone significantly reduced exploratory activity in a novel environment (holeboard). Neither interaction nor additive effects were observed when the two treatments were combined. In contrast, chronic shock increased the immobility in the forced swimming test (behavioral despair) and this effect was completely prevented by concomitant CMI administration. Pituitary-adrenal function was not significantly influenced by any of the treatments. The results indicate that: (a) chronic CMI treatment prevented some but not all behavioral changes caused by chronic shock, and (b) no interaction with basal and stress levels of pituitary-adrenal hormones was observed.
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  • 48
    ISSN: 1432-2072
    Keywords: LY165163 ; Stereotypy ; pCPA ; 5-MeODMT ; Apomorphine ; Serotonin ; Dopamine ; 5-HT1A agonists ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The putative serotonin (5-HT)1A agonist 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluormethylphenyl) piperazine (LY165163, PAPP) induces hyperphagia and hypothermia in rats, but unlike other 5-HT agonists, does not induce 5-HT stereotypy even at high doses (10 mg/kg sc). LY165163 (1 mg/kg) increased striatal DOPA accumulation in animals treated with the aromatic amino acid decarboxylase inhibitor 3-hydroxy-benzylhydrazine (NSD 1015) (100 mg/kg ip). This increase was also found when the drug was given to animals pretreated with parachlorophenylalanine (pCPA) (150 mg/kg ip daily for 3 days). LY165163 (2 and 4 mg/kg sc) inhibited stereotyped behaviour induced by the dopamine (DA) agonist apomorphine (2 mg/kg sc). LY165163 (2, 4, 10 mg/kg sc) also inhibited stereotyped components of the 5-HT syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT; 5 mg/kg ip) which previous studies (e.g. Andrews et al. 1982) suggested to require DA (head weaving, reciprocal forepaw treading). Thus, while other 5-HT1A agonists such as 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) cause stereotypy, this does not occur with LY165163, probably because the drug blocks DA receptors.
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  • 49
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    Psychopharmacology 93 (1987), S. 113-117 
    ISSN: 1432-2072
    Keywords: Ro 5-4864 ; Clonidine ; B-HT 920 ; Guanfacine ; Benzodiazepines ; CL 218, 872 ; Pentobarbitone ; Yohimbine ; Idazoxan ; Convulsions ; Rat ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The protective effect of various alpha2 adrenoceptor agonists such as clonidine, guanfacine, B-HT 920 and ICI 106270 was investigated against Ro 5-4864-induced convulsions in mice and rats. Clonidine and ICI 106270 exhibited a profound anticonvulsant effect while equivalent doses of guanfacine and B-HT 920 were less effective. The anticonvulsant effect of clonidine and ICI 106270 was reversed by pretreatment with yohimbine or idazoxan, indicating the involvement of alpha2 adrenoceptors in their protective effect. Diazepam, clonazepam, CL 218, 872 and pentobarbitone exhibited a different profile of protective action, as these agents protected the animals from apparent mortality as compared to clonidine and ICI 106270 which prolonged the latencies of jerk and convulsion. Modulatory effects of alpha2 adrenoceptors in central GABA function and multiple sites for Ro 5-4864-induced seizures are explained.
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  • 50
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    Psychopharmacology 93 (1987), S. 146-151 
    ISSN: 1432-2072
    Keywords: d-Amphetamine ; Adaptive behaviour ; Operant behaviour ; Decision making ; Water intake ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A complex laboratory task was used to test the effects of low doses of d-amphetamine on decision making in the white rat. In particular, the animals' ability to organize their behaviour into functional sequences was studied. The rats were required to choose between two options in order to obtain rewards (water). To solve the problem efficiently, the animal must correctly use information currently available about the reward probabilities and the response costs of the two activities. The results showed that already at a dose of 0.2 mg/kg, by comparison with control, the decision rule was significantly affected and the efficiency of the behaviour decreased. At 1 mg/kg, the rats were generally unable to organize their behaviour into functional sequences resulting in rewards even though they were able to perform the separate behavioural responses required to solve the task, as shown in separate control experiments. Low doses of d-amphetamine have previously been described to be “psychomotor stimulant” and, for example, to increase locomotion and exploration. Our conclusion is that these low doses do not increase behavioural output in an adaptive way. In simple tasks where motor output is directly related to a measure of performance, these doses might be interpreted as causing increased efficiency. However, when tested in our complex decision making task, these doses result in suboptimal behaviour.
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  • 51
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    Psychopharmacology 93 (1987), S. 182-187 
    ISSN: 1432-2072
    Keywords: Nomifensine ; B-HT 920 ; Dopamine receptors ; Conditioning ; Dopamine-mediated behaviours ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Conditioning of behavioural effects produced by two drugs acting differently upon dopaminergic neurotransmission was studied. Nomifensine and the putative dopamine autoreceptor agonist B-HT 920 produce contrasting effects on motility, namely increases in locomotor activity and stereotypies as compared to hypokinesia and ptosis. The administration of each of these drugs (US) was repeatedly associated with well-defined environmental stimuli (CS): a wire cage associated with an auditory and on olfactory stimulus. The rats were conditioned for 7 days with 20 mg/kg nomifensine IP each day. After conditioning, the rats were treated with the solvent alone in presence of the CS. Not only did sniffing and licking occur, but also gnawing, even though the latter response was not evident after acute administration of the drug or during the conditioning period. Nomifensine (20 mg/kg IP) also acutely decreased the ratio of 3,4-dihydroxyphenylacetic acid/dopamine concentrations (DOPAC/DOPAMINE); this ratio was not altered in the conditioned rats, 60 min after solvent administration in presence of the CS. Rats were conditioned with 0.02 mg/kg IP B-HT 920 daily for 8 days. During the conditioning phase, akinesia and ptosis showed a slight enhancement and a faster onset. After conditioning, when the rats were treated with the solvent alone, the majority of them showed akinesia and/or ptosis during the observation period, in contrast to pseudoconditioned controls. When these rats were conditioned or pseudoconditioned, respectively, with B-HT 920 for further 5 days using 0.02 mg/kg again, treatment with the same dose in presence of the CS produced a significant enhancement and acceleration of these signs in conditioned as compared with pseudoconditioned control rats. The results show that stereotypies producd by nomifensine and akinesia and ptosis produced by B-HT 920 can be conditioned and that, in addition, a sign of stereotypies which was not manifest during the conditioning period appeared as conditioned response.
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  • 52
    ISSN: 1432-2072
    Keywords: Trimethyltin ; Hippocampus ; Learning and memory ; Autoshaping ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The organometal neurotoxin trimethyltin (TMT), induces impaired learning and memory for various tasks. However, administration is also associated with other “non-specific” behavioral changes which may be responsible for effects on conditioned behaviors. To determine if TMT treatment causes a specific learning impairment, three experiments were done using variations of a delay of reinforcement autoshaping task in which rats learn to associate the presentation and retraction of a lever with the delivery of a food pellet reinforcer. No significant effects of TMT treatment were found with a short (4 s) delay of reinforcement, indicating that rats were motivated and had the sensorimotor capacity for learning. When the delay was increased to 6 s, 3.0 or 6.0 mg TMT/kg produced dose-related reductions in behaviors directed towards the lever. Performance of a group given 7.5 mg TMT/kg, while still impaired relative to controls, appeared to be better than the performance of groups given lower doses. This paradoxical effect was investigated with a latent inhibition paradigm, in which rats were pre-exposed to the Skinner boxes for several sessions without delivery of food reinforcement. Control rats showed retardation of autoshaping when food reinforcement was subsequently introduced. Rats given 7.5 mg TMT/kg exhibited elevated levels of lever responding during pre-exposure and autoshaping sessions. The results indicate that 7.5 mg TMT/kg produces learning impairments which are confounded by hyperreactivity to the environment and an inability to suppress behavior toward irrelevant stimuli. In contrast, low doses of TMT cause learning impairments which are not confounded by hyperreactivity, and may prove to be useful models for studying specific associational dysfunctions.
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  • 53
    ISSN: 1432-2072
    Keywords: Yawning ; Apomorphine ; 6-Hydroxydopamine ; Autoreceptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apomorphine-induced yawning was studied in male rats with bilateral 6-hydroxydopamine lesions of the substantia nigra. Apomorphine 10, 20 and 50 μg/kg SC induced dose-dependent yawning in unoperated controls and animals with sham lesions. In the lesioned animals (in which the mean striatal dopamine depletion was 67%), the maximum yawning response rate was greatly attenuated with no evidence that the dose response curve was shifted in either direction. Furthermore, blockade of yawning in the lesioned animals was not simply due to suppression by other stereotyped behaviours, since there was no evidence of increased sniffing or chewing in these animals. These data provide further support for the hypothesis that apomorphine-induced yawning is mediated by dopamine autoreceptors and requires intact nigrostriatal projections.
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  • 54
    ISSN: 1432-2072
    Keywords: 5-HT1A receptors ; Anxiolytics ; Interactions ; Feeding ; Rat ; 5-HT autoreceptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the novel anxiolytics gepirone, buspirone and ipsapirone on free feeding and on feeding induced by the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), were examined. Gepirone dose-dependently increased feeding 2 and 4 h after injection, the magnitude of the response being larger than previously observed with any other 5-HT1A receptor ligand. Previous studies have suggested that buspirone and ipsapirone can block some of the behavioural effects of 8-OH-DPAT. However, gepirone, buspirone and ipsapirone did not inhibit feeding induced by 8-OH-DPAT. These results indicate that gepirone is a very efficacious appetite stimulant in rats and suggest that gepirone, buspirone and ipsapirone act as 5-HT autoreceptor agonists in the feeding model.
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  • 55
    ISSN: 1432-2072
    Keywords: Animal model ; Catalepsy ; Neuroleptics ; Paw test ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An often used animal model based on the effects of neuroleptics on spontaneous behaviour is the catalepsy test. However, this test seems to be particularly insensitive to the atypical neuroleptics thioridazine and, especially, clozapine. We have therefore developed an alternative test, the paw test, which measures the ability of drugs to prevent the spontaneous withdrawal of fore- and hindlimbs in rats, and have compared this with the classical catalepsy test. The results show that: 1) the classical neuroleptic drugs haloperidol and chlorpromazine, the atypical neuroleptic drugs clozapine and thioridazine, the potential atypical neuroleptic drugs molindone and SCH 23390, and the potential classical neuroleptic drug metoclopramide are potent in increasing the hindlimb retraction time; 2) the paw test discriminates between classical neuroleptics which are equipotent in prolonging both the forelimb (FRT) and hindlimb retraction time (HRT) and atypical neuroleptics which are much more potent in prolonging HRT than in prolonging FRT; 3) the non-neuroleptic drugs desipramine, diazepam and morphine do not influence the variables measured in the paw test, although morphine does produce catalepsy; 4) Molindone as well as SCH 23390 behave like atypical neuroleptic drugs in the paw test. In comparison with the classical wood block catalepsy test, the paw test is shown to be superior for predicting the profile of the neuroleptics tested. Although more neuroleptics and non-neuroleptics have to be tested to determine whether false positives and false negatives do occur, we feel that the paw test might be an interesting animal model, because the increase in hindlimb retraction time was associated with the antipsychotic potential, whereas the increase in forelimb retraction time was associated with the potential to induce so-called extrapyramidal side effects.
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  • 56
    ISSN: 1432-2072
    Keywords: Animal model of depression ; DMI ; Stress ; Saccharin ; Sucrose ; Saline ; Preference ; Anhedonia ; Corticosterone ; Glucose ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats exposed chronically (5–9 weeks) to a variety of mild unpredictable stressors showed a reduced consumption of and preference for saccharin or sucrose solutions. Preference deficits took at least 2 weeks to develop and were maintained for more than 2 weeks after termination of the stress regime. Sucrose preference was unaffected by 1 week of treatment with the tricyclic antidepressant DMI but returned to normal after 2–4 weeks of DMI treatment. DMI did not alter sucrose preference in unstressed animals. No significant changes were seen in saline preference either during stress or following drug treatment. DMI reduced blood corticosterone and glucose levels, but stress did not significantly alter either measure. The results are discussed in terms of an animal model of endogenous depression.
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  • 57
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    Psychopharmacology 93 (1987), S. 389-392 
    ISSN: 1432-2072
    Keywords: Microgram doses of diazepam ; Convulsions ; Punishment-induced behavioral suppression ; Mouse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cooper (1983, 1985) observed an inhibition of ambulation and fluid intake in rats following diazepam in the microgram dose range. The present study aimed at investigating the effects of microgram doses of this benzodiazepine on i) the threshold doses of either pentylenetetrazole, picrotoxin or bicuculline required to induce seizures in mice and ii) the suppression of lever pressing for food induced by the delivery of one electric footshock every ten presses in rats pretreated or not with isoniazid (64 mg/kg IP). Diazepam 4–32 μg/kg IP) neither reduced seizure threshold doses of either convulsant studied nor did this drug (16–128 μg/kg IP) reliably decrease the number of lever presses under the punishment schedule. The present study provides no further evidence for a dose-related biphasic effect of diazepam which could give new insight into the functioning of benzodiazepine-coupled brain processes.
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  • 58
    ISSN: 1432-2072
    Keywords: Morphine dependence ; Withdrawal syndrome ; Locus coeruleus ; Norepinephrine, clonidine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Naloxone HCl (10 μg/0.5 ml) was injected in the locus coeruleus (LC) of morphine-dependent rats and the behavioural manifestations of morphine withdrawal and the cortical levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) were measured 30 min later. Naloxone precipitated a withdrawal syndrome and raised cortical MHPG-SO4 in animals made dependent by ascending doses of morphine for 11 days. An injection of clonidine intraperitoneally (200 μg/kg) or in the LC (5 μg/0.5 μl) blocked most aspects of the withdrawal syndrome except jumping and had no effect on the naloxone-induced rise in cortical MHPG-SO4. The findings confirm the hypothesis that the LC is one of the sites where naloxone and clonidine, respectively, precipitate and reduce the narcotic withdrawal syndrome but argue against a role of noradrenergic neurons originating in the LC and innervating the cortex in the ability of clonidine to suppress some aspects of withdrawal syndrome precipitated by naloxone in morphine-dependent animals.
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  • 59
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    Psychopharmacology 92 (1987), S. 478-483 
    ISSN: 1432-2072
    Keywords: Rat ; Marmoset ; Serotonin agonists ; Serotonin antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The actions of the serotonin precursor 5-hydroxytryptophan (5-HTP), the agonist 5-methoxy-N,N-dimetyltryptamine (MeODMT) and quipazine (QPZ) and the antagonists cyproheptadine, methysergide and metergoline, were studied in the rat and in the common marmoset (Callithrix jacchus). The precursor and agonists elicited head shakes, forepaw padding, splayed hindlimbs, tremor and Straub tail in the rat. However, head shakes were not observed after MeODMT and Straub tail was not observed after QPZ. Carbidopa plus 5-HTP potentiated only head shakes, while tranylcypromine (TCP) plus 5-HTP potentiated all the behaviors above. In the marmoset, the action of these drugs elicited drowsiness, teeth chattering, ataxia, vomiting and decreased motor activity, although vomiting was not elicited by MeODMT and ataxia and drowsiness by QPZ. Although TCP plus 5-HTP potentiated all these behaviors, carbidopa plus 5-HTP was not effective. Rats treated with the antagonists (1.0, 5.0 and 10 mg/kg doses) did not show any of these behaviors, but marmosets treated with the same drugs developed “drowsiness”, vomiting, and decreased motor activity; nonetheless, cyproheptadine (5.0 and 10 mg/kg doses) did not elicit “drowsiness”, while increasing motor activity and the number of head shakes. Pretreatment of marmosets with these antagonists blocked only teeth chattering elicited by MeODMT (4.0 mg/kg) and QPZ (10 mg/kg). Pretreatment with haloperidol, p-chlorophenylalanine and α-methyl-P-tyrosine had no effect. The data obtained show that rats and marmosets present differential behavioral responses to the 5-HT drugs used. Marmosets have a richer behavioral repertoire and show greater sensitivity to 5-HT agonists and antagonists. The data suggest that this animal might become a useful biological model for the study of central 5-HT systems.
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  • 60
    ISSN: 1432-2072
    Keywords: Chlordiazepoxide ; Midazolam ; GABA ; R0 15-1788 ; CGS 8216 ; FG 7142 ; Serotonin ; 8-OH-DPAT ; Methysergide ; Amygdala ; Conflict ; Successive discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interactions between the benzodiazepines (BZs) chlordiazepoxide (CDP) and midazolam (MDZ), the BZ antagonist R0 15-1788, the inverse BZ receptor agonists CGS 8216 and FG 7142, γ-aminobutyrate (GABA), serotonin (5-HT), the 5-HT2 antagonist methysergide and the putative 5-HT agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) were investigated using peripheral and intra-amygdaloid treatments. A multiple schedule consisting of rewarded, nonrewarded (Time out: TO) and conflict periods was used to compare in parallel effects on successive discrimination between rewarded and nonrewarded periods and punished responding. The three components were presented in both a fixed order (Experiment 1) and a random order (Experiments 2 and 3). Intra-amygdaloid treatments with GABA and the BZs selectively increased rates of punished responding. CDP given systemically, on the other hand, increased both TO and conflict rates, suggesting an additional impairment of discrimination, which was more marked in the random than the fixed order condition. R0 15-1788, CGS 8216 and FG 7142 given by both routes counteracted the anti-conflict effects of CDP given centrally or systemically. However increases in TO rates induced by IP CDP were antagonized only by IP treatments with these compounds. The two inverse agonists, but not R0 15-1788, also counteracted increases in punished responding which were found after intra-amygdaloid GABA infusions. In Experiments 2 and 3 where baseline rates of pressing in Conflict periods were sufficiently high to detect decreases, CGS 8216 and FG 7142 reduced responding below control level, suggesting a specific anxiogenic activity. Evidence for effects of R0 15-1788 by itself was inconclusive. 5-HT injected into the amygdala also reduced punished responding below control level, whereas methysergide increased it with both central and peripheral treatment. Effects of 8-OH-DPAT varied according to route of administration. With IP treatment Conflict rates were increased, but after amygdaloid infusion both TO and Conflict rates were marginally reduced below control level, with a more consistent depression of punished responding. These results provide evidence that effects of BZs on punished responding are mediated by a GABAergic system which includes the lateral/basolateral amygdala, but which does not participate in BZ-induced disruption of discrimination. They also indicate that the antagonistic effects of CGS 8216 and FG 7142 involve a decrease in GABA transmission, and that these compounds may also be anxiogenic. Finally, the results suggest that 5-HT utilizes the same system for regulating resistance to punishment, but plays no significant part in reward-nonreward successive discrimination, which is impaired after systemic BZs.
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  • 61
    ISSN: 1432-2072
    Keywords: Conflict ; Anxiety ; GABA inhibition ; Epilepsy ; Benzodiazepine antagonist ; Benzodiazepine inverse agonist ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Proconflict and electrocorticographic effects of drugs acting on the benzodiazepine (BDZ)/GABA/chloride-ionophore receptor complex were studied in rats in an attempt to correlate their anxiogenic and epileptogenic activities. Evidence for proconflict activity was assessed by means of an operant conflict procedure based on the simultaneous reward and punishment of a conditioned task, while epileptogenic properties were assessed by monitoring the electrocorticogram (ECoG) of free-moving rats. Pentylenetetrazole and picrotoxin, which act through a site on the chloride channel, and the benzodiazepine (BDZ) inverse agonist FG 7142 showed epileptogenic alterations in the ECoG at doses, respectively, 8, 2 and 3 times higher than those eliciting a significant proconflict effect. For the partial inverse agonist CGS 8216, a ratio of about 60 was found while the BDZ antagonist Ro 15-1788 showed neither epileptogenic nor proconflict activity, except at the highest tested dose for the latter effect (40 mg·kg−1 PO). Inhibition of GABA transmission may mediate both anxiogenic and epileptogenic actions, and a link between these properties may exist as a continuous spectrum of negative intrinsic efficacy at the central BDZ/GABA/chloride-ionophore receptor complex.
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  • 62
    ISSN: 1432-2072
    Keywords: Dopamine receptors ; Striatum ; Denervation ; Supersensitivity ; Subsensitivity ; L-Dopa ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Denervation-induced supersensitivity of the striatal dopamine receptors can be quantified by the turning behaviour induced by apomorphine. With this experimental model we found that high-dose L-dopa/carbidopa administration reduced this supersensitivity. This effect was seen on the 1st day and did not alter over 5 or 10 days of treatment, but dissappeared when medication was discontinued. The degree of reduction was the same, independent of the dose and period of administration. This effect could provide a useful model for studying the phenomenon of the irreversibility of the supersensitivity of the striatal dopamine receptors.
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  • 63
    ISSN: 1432-2072
    Keywords: Ethanol ; Tolerance ; Tail-flick ; Classical conditioning ; Rat ; Antinociception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rats, ethanol increases the latency of the tail-flick reflex to radiant heat. Three experiments examined the contribution of classical conditioning to the acquisition of tolerance to this antinociception. Experiment 1 showed that the antinociception produced by ethanol was dose dependent. The results of Experiment 2 demonstrated that rats exposed to a series of ethanol injections paired with a distinctive environment developed tolerance to this antinociception. In Experiment 3, tolerance was more pronounced in animals that had been exposed to ethanol and tested in the distinctive environment than in animals that had received ethanol in a nondistinctive environment. In contrast to previous reports in the literature, these results show that animals need not practice the tail-flick reflex while intoxicated in order to develop tolerance. Additionally, the data suggest that classical conditioning may contribute to tolerance to the antinociceptive effects of ethanol.
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  • 64
    ISSN: 1432-2072
    Keywords: Anorexia ; Body weight ; Food intake ; Oestradiol benzoate ; Ovariectomy ; Cyproheptadine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Repeated bodily immobilization significantly reduced the food intake of ovariectomized rats. Additionally, immobilization and oestradiol benzoate were found to produce additive effects in depressing feeding. To determine whether serotonergic mechanisms are involved in the stress-and oestrogen-induced anorexia, the 5-HT antagonist cyproheptadine was given to ovariectomized rats that were immobilized and treated with oestradiol benzoate. Cyproheptadine had no effect on the anorexia produced by oestradiol. The food intake of immobilized rats treated with cyproheptadine was similar to control values, suggesting 5-HT involvement in the stress-induced anorexia. However, cyproheptadine had no ameliorating effects on the changes in body weight following immobilization treatment. The implications of these findings are discussed in relation to a possible neuroendocrine basis for anorexia.
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  • 65
    ISSN: 1432-2072
    Keywords: Behavioural tolerance ; Benzodiazepine ; Chlordiazepoxide ; Instrumental learning ; Rat ; Sedation ; Self-stimulation ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sedative and facilitatory effects on variable-interval hypothalamic self-stimulation were monitored during chronic treatment with chlordiazepoxide (CDP; 7.5 mg/kg IP), given at 48-h intervals in two groups of rats. Group 1 was injected immediately before each of 40 1-h self-stimulation sessions (“drugged responding”); Group 2 was injected after self-stimulation for the first 20 sessions (“undrugged responding”), and before self-stimulation for a further 20 sessions (“drugged responding”). Significant sedation occurred in both groups in initial sessions of drugged responding, even though Group 2 had already received 20 injections of CDP (after undrugged sessions). Sedative effects showed very rapid tolerance, and disappeared after 1–3 sessions, but only in rats which had been responding while drugged (and which thus had had opportunities to develop coping strategies against the sedative effects). After further sessions of drugged responding, sedation was replaced by apparently stimulant effects. Stimulant effects showed no tolerance at all in either group even after 40 injections, thus differing from anti-conflict (and other) effects of BZDs, which generally show gradual tolerance. These results show that coping strategies acquired by instrumental learning can account for rapid and selective tolerance to sedative effects. Coping strategies do not account for the differing rates of tolerance to stimulant and to other effects of BZDs; these differences may indicate pharmacologically distinct brain systems downstream from the BZD receptor.
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  • 66
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    Psychopharmacology 93 (1987), S. 243-249 
    ISSN: 1432-2072
    Keywords: Vasopressin ; Desglycinamide-vasopressin ; Amphetamine ; Matching to position ; Memory ; Arousal ; Signal detection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of peripherally injected arginine vasopressin (AVP: 0–25 μg/kg), its desglycinamide analogue (DGAVP: 0–25 μg/kg), which is practically devoid of pressor activity, and d-amphetamine (AMP: 0–1.25 mg/kg) were studied using a delayed (0–32 s) matching to position task (Dunnett 1985). A limited hold for responding (20 s) was in operation. This task enables an accurate assessment of forgetting in rats. AVP reliably improved per cent correct performance, and this effect was substantiated by accuracy indices derived from signal detection theory (TSD). DGAVP, however, was inactive, suggesting that the parent peptide's pressor properties were responsible for its beneficial effects. AMP disrupted performance in a dose-related manner, and was the only substance to alter a TSD bias index (responsivity index, RI), indicating a degree of response repetition at the highest dose. These results are consistent with some earlier reports, and suggest that AVP may enhance memory by peripheral action, while AMP disrupts performance. Closer inspection of the data, however, suggested that the peptide reduced general responsiveness. A new index to measure bias (Sahgal 1987) suggested that AVP-treated subjects restricted their sample and choice responses to one side of the operant chamber, thereby achieving a spuriously high detection rate with few errors of commission (incorrect responses). It is concluded that AVP does not, after all, improve performance: on the contrary it has detrimental effects, and produces errors of omission (failure to respond).
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  • 67
    ISSN: 1432-2072
    Keywords: d-Amphetamine ; Simultaneous discrimination ; Control by S+ and S− ; General transfer ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained in a Y-maze on a two-choice simultaneous black-white discrimination with either black or white as S+. Animals were then transferred to one of three discrimination tasks. In task 1 (New S−), a new stimulus, either vertical or horizontal stripes, was substituted for the original S−. In task 2 (New S+), a new stimulus, either vertical or horizontal stripes as in task 1, was substituted for the original S+. In task 3 (New S+/S−) animals were trained on horizontal-vertical discrimination. The pre-trial administration of 1 mg/kg d-amphetamine facilitated the acquisition of the original black-white discrimination with both black as S+ and white as S+. Likewise, the drug improved performance in all three transfer conditions. However, the course of learning in the three transfer tasks was different in the placebo- and amphetamine-treated animals. Amphetamine-treated animals were disrupted more by a change in S+ than by a change in S−, whereas the opposite pattern was evident in the placebo controls. When both discriminative stimuli were changed, placebo animals exhibited pronounced decrement in performance, whereas amphetamine animals exhibited excellent learning. The implications of these findings for the effects of amphetamine on discrimination learning are discussed.
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  • 68
    ISSN: 1432-2013
    Keywords: Cortical collecting tubule ; Rat ; ADH ; Principal cells ; Intercalated cells ; Barium ; Amiloride ; Ouabain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanism of ion transport across principal cells of rat cortical collecting tubules (CCT) and its regulation by vasopressin (ADH) has been studied in the isolated perfused tubule. To amplify the response to ADH rats were treated with 5 mg I. M. desoxycorticosterone 4–9 days prior to the experiments. Addition of 2·10−10 mol·1−1 ADH increased the transepithelial voltage from −5.1 ±0.7 mV to −16.1±1.4 mV (n=37) and decreased the transepithelial resistance from 51±4 Ω cm2 to 39±2 Ω cm2 (n=33). Optical and functional differentiation of impalements of principal and intercalated cells was made and only data of principal cells are presented. ADH depolarized the apical membrane from 79±1 mV to 66±2 mV (n=26) and decreased the fractional resistance of the apical membrane from 0.76±0.04 to 0.70±0.04 (n=13). These ADH effects were prevented by 10−5 or 10−4 mol·1−1 luminal amiloride which hyperpolarized the apical membrane when added in the presence or absence of ADH. Apical and basolateral membranes were dominated by large K+ conductances and addition of 3 mmol·1−1 barium to bath or lumen perfusates increased transepithelial resistance almost two-fold, whereas luminal amiloride increased the transepithelial resistance only by 26–35%. Ouabain (0.5 mmol·1−1, bath) depolarized the basolateral membrane and decreased its K+ conductance. These effects were prevented by the simultaneous presence of apical amiloride suggesting that the only route of Na+ entry into the principal cells occurred via the amiloride sensitive Na+ conductance. We conclude that ADH stimulates Na+ reabsorption and K+ secretion in the rat CCT primarily by increasing the Na+ conductance in the apical cell membrane.
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  • 69
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    Pflügers Archiv 409 (1987), S. 507-511 
    ISSN: 1432-2013
    Keywords: Vestibulo-ocular reflex ; Rat ; Serotonin ; Agonists and antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of intraventricular injection of serotonin (5-HT) and its agonists and antagonists on the amplitude of the vestibulo-ocular reflex were studied in chronic implanted rats. 5-HT (10−5 M) triggers an increase of the amplitude of the reflex which lasts 30 min. Similar results are obtained when N,N-dimethyl-5-methoxytryptamine (10−3 M) is introduced into the ventricular cannula. The increasing effects observed both with 5-HT and N,N-dimethyl-5-methyoxy-tryptamine are abolished by methiothepin, a potent antagonist of 5-HT receptors. Injection of indirect agonists like pargyline, a monoamine oxidase inhibitor, or fluoxetine, a potent inhibibitor of 5-HT reuptake, is followed by an increase of the amplitude of the vestibulo-ocular reflex. These results indicate that 5-HT can modulate the activity of the vestibulo-ocular pathway and muscular tone of extraocular muscles. Location and involvement of various modulating 5-HT sites are discussed.
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  • 70
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    Pflügers Archiv 409 (1987), S. 194-199 
    ISSN: 1432-2013
    Keywords: Sodium transport ; Amiloride ; Colon ; Rat ; Ontogeny
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate developmental changes in colonic sodium transport, the sensitivity of the transepithelial potential and short-circuit current to amiloride was investigated. The amiloride-sensitive short-circuit current (I sc Na ), which represents the electrogenic sodium transport through Na+ channels, rose significantly from day 5, reached a peak on day 10, and entirely disappeared after weaning. The maximum rate of electrogenic, amiloride-sensitive sodium transport was 12.0 μEq/cm2 · h. TheI sc Na was suppressed by adrenalectomy and/or premature weaning but not by a mineralocorticoid antagonist, spironolactone. On the contrary, treatments which increase aldosterone levels in vivo (low-sodium diet, furosemide-induced natriuresis, high dietary intake of potassium) stimulated theI sc Na . The effect of adrenalectomy increased during postnatal development. The sensitivity ofI sc Na to aldosterone was highest at the end of the weaning period. High-sodium diet, which causes a decrease in circulating aldosterone, was associated with a partial inhibition ofI sc Na (P〈0.016). These data suggest that the distal colon of neonatal rats can transport sodium via an electrogenic, amiloride-sensitive mechanism and that adrenocortical hormones exert the main regulatory control of this pathway.
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  • 71
    ISSN: 1432-1912
    Keywords: Substance P ; Neurokinin A ; Intrathecal injection ; Sciatic nerve transection ; Scratching, biting and licking response ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of unilateral sciatic nerve transection on behavioural responses produced by intrathecal administration of substance P (SP), neurokinin A, eledoisin and physalaemin was investigated in the rat. The injection of SP (3 nmol/rat) into the subarachnoid space was followed by reciprocal scratching, biting and licking of the fore- and hind-limbs. There was no observable difference in the behavioural response to SP between rats with nerve transection and sham operated rats at 5 days after operation. Whereas at 10, 20, and 30 days after nerve transection the response to SP was significantly increased as compared with sham operated rats. This phenomenon was also observed with neurokinin A (1.5, 3.0 and 6.0 nmol/rat), eledoisin (0.05 and 0.10 nmol/rat) and physalaemin (0.05 and 0.10 nmol/ rat) at 10 days after operation. Ipsilateral depletion of SP from the lumbar (L4-L6) spinal cord was observed at 5, 10, 20, and 30 days after the unilateral transection of the sciatic nerve. These results suggest that sciatic nerve transection may produce an increased response to tachykinins through an enhanced sensitivity of tachykinin receptors in the lumbar cord.
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  • 72
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    Naunyn-Schmiedeberg's archives of pharmacology 336 (1987), S. 670-676 
    ISSN: 1432-1912
    Keywords: Vascular smooth muscle ; Calcium entry blockers ; Rat ; Depolarisation ; Serotonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of the calcium entry blockers verapamil (V), diltiazem (D), nifedipine (NF) and nicardipine (NC) have been studied on calcium concentration-effect curves elicited in depolarized (K+, 40 mmol/l) and in serotonin-exposed (6 μmol/l) rat middle cerebral arteries (RMCA) in order to compare the relative potencies of the blockers against these two calcium channel activating mechanisms. In control conditions, Ca2+ sensitivity expressed as pD2 and maximal active wall tension (AWT) were not significantly different in depolarized and in 5-HT-exposed vessels: pD2: 3.39 ±0.08 vs 3.50 ± 0.06 and AWT: 0.93 ± 0.15 mN · mm−1 vs 0.90 ± 0.16 mN · mm−1 respectively. V, D, NF and NC displaced Ca2+ control curves to the right and depressed the maximum contractile response in the two experimental conditions, which suggests a noncompetitive type of antagonism. All the blockers were more potent inhibitors of Ca2+-induced contractions in depolarized than in serotonin-exposed middle cerebral arteries. The IC50 values (concentration of blockers producing a 50% inhibition of maximal control contractile response) were (nmol/l) : V = 20, D = 120, NF = 0.4, NC = 1 and V = 400, D = 10000, NF = 20, NC = 7 in depolarized and serotonin-exposed arteries respectively. From these IC50 values, the relative order of potency of the CEB's was not the same in the two experimental conditions suggesting that while serotonin and K+ both promote the entry of Ca2+ into vascular smooth muscle cells of RMCA, they either activate a different gating mechanism associated with a single common channel or perhaps distinct channels. Comparison of the results obtained in this study for depolarized rat middle cerebral arteries with those previously obtained in depolarized rat mesenteric resistance arteries (RMRA) revealed that while Ca2+-induced contractile responses were inhibited in a similar non-competitive manner by the four CEB's, the respective IC50 values showed that potencies and rank of relative potency of the blockers were different in the two types of vessels. D and NC were equally potent in both preparations (IC50 ratio = 2.5 and 3 respectively) but RMCA were more sensitive to V and NF than RMRA (IC50 ratio = 6.5 and 11 respectively). These results are discussed and it is proposed that regional differencies in the conformation and/or the activation of the voltage-gated Ca2+ channels may exist in different vascular beds.
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  • 73
    ISSN: 1432-1912
    Keywords: (±)-Baclofen ; Micturition reflexes ; Rat ; Pelvic ganglia ; GABA B receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effect of (±)-baclofen on micturition reflexes was investigated in urethane-anaesthetized rats. A ‘low’ dose of (±)-baclofen (0.5 mg/kg i.v.) barely affected the early phase of the transurethral cystometrogram (CMG) which involves activation of a spinal vesico-vesical excitatory reflex. 2. At a higher dose (2.5 mg/kg i.v.) (±)-baclofen suppressed both the spinal and supraspinal components of the bladder response to transurethral saline filling. 3. When the bladder was filled by the transvesical route a series of regular voiding cycles was obtained which are due to activation of a supraspinal vesico-vesical excitatory reflex. In this model, voiding efficiency of the rat bladder was markedly reduced even after a low dose of (±)-baclofen (0.5 mg/kg) and almost suppressed at 2.5 mg/kg. 4. (±)-Baclofen reduction of voiding efficiency was mainly ascribable to an inhibitory effect on the expulsive phase of the voiding cycle which, in rats, depends critically upon the activation of a reflex which induces a twitch-like contraction of urethral/periurethral skeletal muscles. 5. (±)-Baclofen produced a small inhibition of the pinching-induced somatovesical excitatory reflex. (±)-Baclofen (2.5 mg/kg i.v.) produced also a marked but transient inhibition of bladder contractions induced by preganglionic nerve stimulation. However the time course of this effect was markedly shorter as compared to the long lasting suppression of voiding cycle observed with this same dose of the drug. 6. (−)-Baclofen, which is more potent than (±)-baclofen as a GABA B receptor agonist, affected bladder response to transurethral or transvesical filling in a manner similar to that observed with the racemate, but at lower doses (0.1–0.5 mg/kg i.v.). 7. These findings indicate that: a) (±)-baclofen affects markedly various types of reflexes concerned with micturition; b) a central site seems the main determinant of its action; c) at a low dose level inhibition of the reflex activation of urethral/periurethral skeletal muscles rather than the detrusor is a main target for (±)-baclofen action and d) GABA B receptors may modulate excitatory neurotransmission in rat pelvic ganglia.
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  • 74
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    Naunyn-Schmiedeberg's archives of pharmacology 335 (1987), S. 255-260 
    ISSN: 1432-1912
    Keywords: Tyramine ; Neuropeptide Y ; Calcium-independence ; Desipramine ; Norepinephrine ; Vas deferens ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of tyramine on the isolated vas deferens of rats was investigated. Tyramine induced a dose-dependent contraction which was blocked by phentolamine and disappeared in adrenergic denervated tissues. In the presence of an antiserum to neuropeptide Y (NPY), the contraction induced by concentrations of tyramine greater than 10 μM was markedly increased. In addition to inducing the release of 3H-norepinephrine (NE), tyramine evoked a concentration-dependent efflux of NPY-like immunoreactivity (NPYLI) from synaptosomal preparations. This action was not modified either by the removal of calcium ion from the medium or by the pretreatment with tetrodotoxin (0.5 μM). Desipramine suppressed the NPY-LI release induced by tyramine apparently by the inhibition of the uptake of tyramine is suggested by the significant positive correlation between the reduction of 4C-tyramine uptake and the inhibition of NPY-LI release induced by desipramine (r = 0.946). Therefore, we suggest that tyramine does induce the release of NPY from rat vas deferens, in addition to effecting NE secretion.
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  • 75
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    Pediatric nephrology 1 (1987), S. 498-501 
    ISSN: 1432-198X
    Keywords: Hydronephrosis ; Vasoconstriction ; Renin-angiotensin system ; Prostaglandins ; Indomethacin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the effects of inhibition of either prostaglandins or the role of prostanoids and the renin-angiotensin system on renal function in rats with congenital unilateral hydronephrosis. Wistar rats with congenital unilateral hydronephrosis were infused with normal saline (control), captopril dissolved in normal saline or indomethacin dissolved in a solution of sodium chloride and sodium carbonate. In the control group both glomerular filtration rate (GFR) and effective renal plasma flow were reduced in the right hydronephrotic kidney (RHK) compared with the normal left kidney. Indomethacin did not improve renal function in the RHK. Captopril significantly improved GFR in the RHK. These results support the conclusion that the renin-angiotensin system is an important mediator of reduced GFR in congenital unilateral hydronephrosis in rats.
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  • 76
    ISSN: 1432-1106
    Keywords: Peptides ; Coexistence ; Nucleus tractussolitarii ; Ventral medulla ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The medulla oblongata and pons of colchicine treated rats were analyzed with a doublestaining technique using mouse monoclonal antibodies to somatostatin and rabbit polyclonal antibodies raised against methionine-enkephalin. Numerous cells reacted with both antisera but cells reacting with only one antiserum were also observed. Double-stained cells were most frequently encountered at all levels of the nucleus tractus solitarii, in a well defined group in the caudal medullary reticular formation, along the lateral ventral surface of the medulla oblongata, dorsolateral to the inferior olive and in the nucleus raphe magnus. These findings provide further examples of coexistence of two peptides and indicate the possibility that somatostatin-and enkephalin-like peptides are co-released.
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    Experimental brain research 68 (1987), S. 1-27 
    ISSN: 1432-1106
    Keywords: Hippocampus ; Single unit activity ; Spatial memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Single unit activity was recorded from complex spike cells in the hippocampus of the rat while the animal was performing a spatial memory task. The task required the animal to choose the correct arm of a 4 arm plus-shaped maze in order to obtain reward. The location of the goal arm was varied from trial to trial and was identified by 6 controlled spatial cues which were distributed around the enclosure and which were rotated in step with the goal. On some trials these spatial cues were present throughout the trial (spatial reference memory trials) while on other trials they were present during the first part of the trial but were removed before the rat was allowed to choose the goal (spatial working memory trials). On these latter trials the animal had to remember the location of the cues and/or goal during the delay in order to choose correctly. 55 units were recorded during sufficient reference memory trials for the relationship between their firing pattern and different spatial aspects of the environment to be determined. 33 units had fields with significant relations to the controlled cues while 16 had significant relations to the static background cues, those cues in the environment which did not change position from trial to trial. Of 43 units which could be tested for their relation to the shape of the maze arms themselves, 15 showed such a relationship. Therefore the place units can be influenced by different aspects of the spatial environment but those related to the task requirement appear to be more potent. Interaction effects between the different spatial factors also influenced the firing pattern of some units. Of particular interest was the interaction between the controlled cues and the static background cues found in some cells since this might shed some light on how the hippocampus enables the rat to solve the memory task. 30 units with place fields related to the controlled cues were recorded during successful performance on spatial working memory trials as well as during spatial reference memory trials. The place fields of 90% of these units were maintained during the retention phase of the memory trials. During the recording of some units, other types of trial were given as well. On control trials, the cues were removed before the rat was placed on the maze. These trials provided controls for the potential influence of information left behind by the controlled cues and for the influence of the animal's behaviour on the unit activity. They also provided information about the unit firing in the absence of the controlled spatial cues and about the animal's choice of goal under these circumstances. During control trials, the units typically maintained their place fields but these fields had no relation to the experimenter-defined goal. The rat's choice of goal arm at the end of the trial, however, continued to show the usual spatial relationship to the fields. The data from these control trials, taken together with the interaction between the controlled cues and the static background cues seen in some of the cells and the characteristic mistakes made by each rat, suggest that the animal enters the task on each trial with an expected or preferred orientation of the controlled spatial cues relative to the background cues and that it must reorient its cognitive map of the environment or search for a different map when the actual orientation of the controlled cues departs from this default condition. Detour trials differed from working memory trials in that the animal was not immediately allowed to choose the goal at the end of the retention period but was forced to enter a non-goal arm instead. These trials ruled out the possibility that the animal was remembering the specific turn required to reach the goal and demonstrated that the place fields for the entire maze are set up as a result of exposure to the controlled spatial cues in any one of the start arms. Overall, the results provide strong support for the cognitive map theory of hippocampal function. In particular, they demonstrate that the representations of places within an environment are connected together to form a map, that the orientation of this map relative to an environment can be changed from trial to trial, and that this orientation is “remembered” following the removal of the controlled spatial cues.
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  • 78
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    Keywords: Dexamphetamine ; Chlordiazepoxide mixtures ; Locomotor activity ; Dopamine ; Lithium ; Striatum ; Animal model of “mania” ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dexamphetamine (DEX) and chlordiazepoxide (CDZP) given together as mixtures have previously been shown to induce a characteristic “compulsive” form of locomotor hyperactivity in rats placed in unfamiliar environments, which was much greater than activity obtained with any dose of either drug given separately; acute pretreatment with lithium counteracted mixture-induced hyperactivity. The role of dopamine in these effects was investigated by measuring concurrently the levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. DEX (0.02-2 mg kg-1) increased horizontal (entries) and vertical (rears) activity, and increased DA and decreased DOPAC and HVA in the striatum. Chlordiazepoxide (CDZP) (12.5 or 20 mg kg-1) increased horizontal activity but did not affect vertical activity or DA or its metabolites. Lithium by itself in acute (2 meq kg-1, 24 and 4 h before test) or extended (2 meq kg-1 daily for 9 days) dosage had little effect on horizontal or vertical activity or levels of DA or DOPAC. Given together, DEX and CDZP (1.18 mg kg-1 + 12.5 mg kg-1), as expected, increased entries much more than did either drug given separately, but rears and levels of DA and metabolites remained similar to those with DEX given alone. Acute lithium pretreatment counteracted the mixture-induced increase in entries. Neither acute nor extended lithium pretreatment significantly altered DEX-induced changes in activity or levels of DA or DOPAC. The results suggest that an action on striatal DA neurones is responsible neither for the increases in entries seen after CDZP and CDZP/DEX mixtures (compared with DEX alone), nor for the attenuating effect of acute lithium on the mixture-induced increases. The changes in vertical activity (rearing) observed with DEX alone may, however, reflect an action on DA neurones. Animal models of “mania” are discussed.
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  • 79
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    Psychopharmacology 91 (1987), S. 209-212 
    ISSN: 1432-2072
    Keywords: Intracerebral drug application ; Memory ; N. raphé magnus ; Clorgyline ; Pargyline ; Deprenyl ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Conditioned taste aversion (CTA) elicited by systemic or intracerebral application of the monoamine oxidase inhibitors clorgyline (C), pargyline (P) or deprenyl (D) was studied in 402 rats. Water-deprived animals were allowed 15 min access to 0.1% sodium saccharin (CS) followed 10 min later by IP or by intracerebral injection of the drug. In the latter case, the animals were anesthetized 5 min after saccharin drinking with pentobarbital and the drug was stereotaxically injected (1 μl/min, 1–2 μl) into the target structure. CTA was assessed in a two-choice retention test performed 2 days later. A geometric progression of three to six dosages applied to groups of rats (n=10) was employed to establish the effective doses of the drugs which were 4, 20 and 32 mg/kg with IP and 2.5, 10 and 80 μg per rat with intracerebral (n. raphé magnus) injections of C, P, and D, respectively. The ratios of intracerebral to systemic dosages eliciting comparable CTA were 1:300 for C, 1:800 for P and 1:100 for D. Injections of 2.5 μg C and 10 μg P into the mesencephalic reticular formation, medial hypothalamus and cerebral cortex were ineffective, as were injections of 10 μg P into the nucleus of the solitary tract and cerebellum. The results indicate that CTA is elicited more efficiently by inhibition of monoamine oxidase A (selectively inhibited by C) than of monoamine oxidase B (selectively inhibited by D).
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  • 80
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    Psychopharmacology 91 (1987), S. 248-253 
    ISSN: 1432-2072
    Keywords: Haloperidol ; Latent inhibition ; Conditioned ; suppression ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Latent inhibition (LI) is a behavioral paradigm in which prior exposure to a stimulus not followed by reinforcement retards subsequent conditioning to that stimulus when it is paired with reinforcement. Two experiments investigated the effects of 0.1 mg/kg haloperidol administration on LI as a function of number of CS pre-exposures. The investigation was carried out using a conditioned emotional response (CER) procedure consisting of three stages: pre-exposure, in which the to-be-conditioned stimulus, tone, was repeatedly presented without reinforcement; conditioning, in which the pre-exposed stimulus was paired with shock; and test, where LI was indexed by animals' suppression of licking during tone presentation. The three stages were conducted 24 h apart. In Experiment 1, 40 CS pre-exposures were given. LI was obtained in both the placebo and haloperidol conditions, but the effect was much more pronounced under the drug. Experiment 2 used ten CS pre-exposures. LI was not obtained in the placebo animals but was clearly evident in animals injected with haloperidol. The implications of these findings for the effects of neuroleptics on learning are discussed.
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  • 81
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    Psychopharmacology 91 (1987), S. 316-319 
    ISSN: 1432-2072
    Keywords: Methamphetamine ; Sensitization ; Ontogeny ; Autoreceptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioral effect of repeated methamphetamine (MAP) treatment was observed in young rat to establish the ontogenetic period crucial to methamphetamine sensitization. Animals were treated with MAP (2 mg/kg, SC) once daily for 5 days (Group 1: postnatal days 2–6, G-2: 7–11, G-3: 12–16, G-4: 17–21, G-5: 22–26, G-6: 27–31). Control animals were similarly treated with an equal volume of saline. On the 35th postnatal day, all rats were challenged with MAP (2 mg/kg, IP). Behavioral sensitization to MAP was not found in G-1, G-2, G-3 or G-4, although responsiveness to MAP was observed in rats after the 2nd postnatal day. The animals in G-5 and G-6 showed hypersensitivity to MAP in locomotor activity and stereotyped behavior. These findings indicate that the period crucial to behavioral sensitization to MAP corresponds to the period of presynaptic dopamine autoreceptor formation in the rat brain.
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  • 82
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    Psychopharmacology 91 (1987), S. 330-333 
    ISSN: 1432-2072
    Keywords: Yawning ; D1 and D2 DA receptors ; DA agonists ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The subtype of dopamine (DA) receptors mediating the yawning response to DA agonists was determined in rats. Yawning was elicited both by the mixed D1–D2 agonist apomorphine and by the specific D2 agonist LY 171555, but not by the selective D1 agonist SKF 38393. Both apomorphine- and LY 171555-induced yawning were antagonized not only by the selective D2 antagonist sulpiride but, unexpectedly, also by the selective D1 antagonist SCH 23390. The results suggest that DA receptors mediating the yawning response are of the D2 type, and that these receptors are connected with D1 receptors in such a way that the blockade of the latter results in the functional inactivation of the former.
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  • 83
    ISSN: 1432-2072
    Keywords: SK & F 38393 ; Behavioural assessment ; Stereotypy ; Behavioural check list ; Grooming ; Dopamine ; Apomorphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioural effects of the D-1 dopamine receptor agonist SK & F 38393 were assessed in the intact adult rat using a conventional stereotypy rating scale and a rapid time sampling behavioural check list procedure. This combination technique allowed description of the nature of any behavioural response and quantification of the number of counts of individual behaviours. Using this combined procedure, SK & F 38393 clearly failed to induce typical stereotyped behaviour. However, in the well-habituated animal, SK & F 38393 dose-dependently increased the number of recordings of non-stereotyped sniffing, locomotion and grooming; some occasional rearing was also noted. An unusual pattern of intense grooming behaviour was a characteristic response to this drug. Using the resolved R-and S-enantiomers of SK & F 38393, promotion of sniffing, locomotion, rearing and grooming resided stereoselectively in the R-configuration. Under appropriate experimental conditions, specifically a requirement for prolonged habituation and the use of a rapid sampling behavioural check list to supplement the rating scale, it is possible to demonstrate that SK & F 38393 is behaviourally active in the whole animal.
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  • 84
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    Keywords: Methiothepin ; 2-Deoxy-d-glucose ; Glucose utilization ; Brain metabolism ; Behavior ; Serotonin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic [14C]2-deoxy-d-glucose method, in 92 discrete brain regions of awake rats, at 1, 2, 3, or 4 h after administration of the serotonergic antagonist methiothepin 0.1 mg/kg IP. The drug produced a cataleptic behavior that peaked in intensity at 3 h after its administration. LCGU declined significantly in 35% of the 92 regions at one or more time points after methiothepin administration. No area of increased metabolism was found. The time-course of the decline in LCGU closely paralleled the intensity of catalepsy; the peak effect was at 3 h, when LCGU was significantly reduced in 32% of the regions examined (mean decline for all regions was 15%). Metabolic depression after methiothepin was most notable in the forebrain, where LCGU declined in many regions of the cerebral cortex, basal ganglia, and thalamus. Most of the regions affected by methiothepin possess a substantial number of serotonin receptors, although LCGU was also reduced in a few regions not primarily involved in serotonergic neurotransmission.
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  • 85
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    Psychopharmacology 92 (1987), S. 376-381 
    ISSN: 1432-2072
    Keywords: Conditioned place aversion ; Nicotine ; Rat ; Time-course ; Dose-response ; Chlorisondamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats received subcutaneous injections of either nicotine (NIC; 0.05–0.8 mg/kg) or vehicle [VEH (phosphate buffer); 1 ml/kg] immediately after conditioning sessions in a place-conditioning paradigm (delay conditioning). NIC was paired for three delay-conditioning sessions with one environment of a three-compartment place-conditioning apparatus; VEH was paired with another environment. The subjects were then tested for place preference or aversion by determining the proportion of time spent in each compartment during a 15-min test session. Delay conditioning with NIC only produced a dose-related place aversion (greater time was spent in the VEH-paired chamber on test day). Place aversion was evident when NIC, 0.8 mg/kg, was administered either immediately or 5 min after conditioning sessions but not when given 15 min after conditioning. Chlorisondamine (5 μg, lateral ventricle), but not saline, administered 2 weeks prior to delay conditioning with 0.8 mg/kg NIC completely blocked the NIC-induced place aversion. These data suggest that delay conditioning with NIC produces place aversion by a central mechanism. Since standard conditioning (NIC injection immediately before the place-conditioning sessions) with NIC only produced dose-related place preferences (Fudala et al. 1985; Fudala and Iwamoto 1986), the time of administration of the unconditioned stimulus is a strong determinant of the place-conditioning effects of NIC.
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  • 86
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    Psychopharmacology 91 (1987), S. 345-351 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Latent inhibition ; Conditioned suppression ; Animal model of schizophrenia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Latent inhibition (LI) is a behavioral paradigm in which animals learn to ignore a repeatedly presented stimulus not followed by meaningful consequences. We previously reported that LI was disrupted following the administration of 1.5 mg/kg dl-amphetamine. The present experiments investigated the effects of 6 mg/kg dl-amphetamine administration on LI in a conditioned emotional response (CER) procedure consisting of three stages: pre-exposure, in which the to-be-conditioned stimulus, tone, was repeatedly presented without reinforcement; conditioning, in which the pre-exposed stimulus was paired with shock; and test, where LI was indexed by animals' suppression of licking during tone presentation. The three stages were conducted 24 h apart. In Experiment 1, the drug was administered in a 2×2 design, i.e. drug-no drug in pre-exposure and drug-no drug in conditioning. LI was obtained in all conditions. In Experiment 2, animals were given either 5 days of 6 mg/kg amphetamine pretreatment and amphetamine in pre-exposure and conditioning or 7 days of saline. LI was not obtained under amphetamine, but this outcome reflected a state-dependency effect. In Experiment 3, animals received either 5 days of amphetamine pretreatment and amphetamine in pre-exposure, conditioning and test or 8 days of saline. LI was obtained in both the placebo and amphetamine conditions. Experiments 4a and 4b compared the effects of two drug doses, 1.5 (4a) and 6 mg/kg (4b), administered in pre-exposure and conditioning. LI was abolished with the 1.5 mg/kg dose but not with the 6 mg/kg dose.
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  • 87
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    Psychopharmacology 91 (1987), S. 363-368 
    ISSN: 1432-2072
    Keywords: Memory ; Neuropeptides ; Vasopressin ; Oxytocin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adult male rats spend a great amount of time investigating novel juveniles. In contrast, rats re-exposed to the same juvenile 30 min after the initial exposure display little investigatory behavior. If the re-exposure occurs 2 h later, the juvenile is thoroughly investigated. These results have been interpreted to mean that rats form a transient memory for a particular juvenile. In the present study, memory was enhanced when the initial exposure to the juvenile was followed by another exposure to the same juvenile (retroactive facilitation) and impaired when exposure to the original juvenile was followed by exposure to another juvenile (retroactive interference). Arginine vasopressin had retroactive facilitating effects on social memory and these effects were blocked by the vasopressor antagonist dPTyr(Me)AVP. Moreover, the antagonist had retroactive interfering effects, since it impaired the recognition of a familiar juvenile. Oxytocin shared the same inhibitory pattern of action. These results suggest that neurohypophyseal peptides may have a prepotent role in modulating the mnemonic processing of chemosensory information associated with social interactions.
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  • 88
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    Psychopharmacology 92 (1987), S. 96-99 
    ISSN: 1432-2072
    Keywords: 5-HT ; l-5-HTP ; Anxiolytic ; Anxiogenic ; Drinking ; Conflict ; Vogel test ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of l-5-HTP (25–400 mg/kg IP) following inhibition of the peripheral aromatic amino acid decarboxylase by means of benserazide (25 mg/kg IP) was investigated in a test modified from Vogel's drinking conflict model. At 50 mg/kg an anti-conflict action was detected, while higher doses (100–400 mg/kg) decreased punished responding. A lower dose (25 mg/kg) had no effect. Non-specific effects — such as alterations in muscle tone, in motivation to drink or in the sensitivity to electrical shock — could not explain the anxiolytic- and anxiogenic-like actions of 50 and 100 mg/kg, respectively. The bi-phasic effect of l-5-HTP is discussed in terms of different subpopulations of central serotoninergic receptors, possibly exerting opposing influences on conflict responding. The study emphasises the importance of 5-HT mechanisms in anxiety, and the possibility of finding novel anxiolytics among drugs selectively affecting central 5-HT neurotransmission.
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  • 89
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    Psychopharmacology 92 (1987), S. 215-218 
    ISSN: 1432-2072
    Keywords: Ethanol ; Naloxone ; Locomotor activity ; Open field ; Active avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The action of naloxone (0.5 and 2 mg/kg IP) on the behavioural effects of a low (2 g/kg PO) and a high dose (4 g/kg PO) of ethanol was studied in rats. Ethanol at the low dose increased spontaneous motility, enhancing open-field external ambulations and reducing shuttle-box latency. All these effects were antagonized by naloxone. Ethanol at the high dose produced hypomotility, decreasing open-field external ambulations and impairing shuttle-box performance. In this case, naloxone also reduced the ethanol effect, but its action was less consistent. Therefore, although mechanisms other than a specific opioid receptor blockade by naloxone must be considered, an involvement of opioid peptides in the effects of ethanol cannot be discounted.
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  • 90
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    Psychopharmacology 93 (1987), S. 477-482 
    ISSN: 1432-2072
    Keywords: Cis-flupentixol ; Reinforced responding ; Motor effects ; Reinforcement efficacy ; Dopamine receptors (D1 and D2) ; Matching law equation ; Variable-interval schedule ; Water reinforcement ; Lever press ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the effects of cis-flupentixol on reinforced responding. The experimental subjects were rats and the reinforced response was a lever press. The procedure was a five-component multiple schedule that provided five different reinforcement rates. Cis-flupentixol produced dose-dependent decreases in reinforced responding. An equation, the matching law, was fitted to the results. One parameter of this equation represents the estimated response rate asymptote. Cis-flupentixol produced dose-dependent decreases in the asymptotes. A second parameter of the equation represents the rate of reinforcement that maintains a one-half asymptotic response rate. Cis-flupentixol did not appear to affect this measure. There is evidence that the response rate asymptote measures motor components of response rate and that the reinforcement parameter measures the efficacy of the reinforcement maintaining the response. According to these results, cis-flupentixol systematically affected the motor-component of reinforced responding — it slowed down lever pressing — without affecting the subject's sensitivity to the reinforcer maintaining the response. In contrast, other neuroleptics have decreased the subjects' sensitivity to reinforcement, according to the matching law measures.
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  • 91
    ISSN: 1432-2072
    Keywords: Dopamine (DA) ; D-1 DA receptor agonist (SK&F 38393) ; D-2 DA autoreceptor agonist (B-HT 920) ; Combination ; Postsynaptic DA receptor-induced stereotyped behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Postsynaptic dopaminergic behavioural effects of D-2 agonists can be promoted by concomitant D-1 receptor activation. The present experiment explored whether such effects could be elicited by the putative autoreceptor-selective D-2 agonist B-HT 920, when combined with the D-1 agonist SK&F 38393. Except for occasional jerks induced by B-HT 920, neither agonist caused significant dopaminergic stimulation when given separately, whereas combined treatment with SK&F 38393 and B-HT 920 induced clear-cut motor activation — particularly focused stereotyped licking and sniffing — in reserpine/AMT-pretreated rats. Both the D-1 antagonist SCH 23390 and the D-2 antagonist spiperone abolished these effects, while the SK&F/B-HT-induced stimulation was not significantly affected by the alpha2-blocker idazoxan. It appears that classical postsynaptic DA receptor-stimulatory properties of B-HT 920 can indeed be demonstrated, provided that sufficient D-1 receptor tone prevails.
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  • 92
    ISSN: 1432-2072
    Keywords: Diazepam ; Water intake ; Holeboard behaviour ; Decision making ; Operant behaviour ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Benzodiazepines, used in the clinic as anxiolytics, have in animal models been found specifically to attenuate behavioural suppression caused by response contigent aversive stimuli, non-reward or novelty. The effects have been interpreted in more general terms as “behavioural disinhibition” or “response perseveration” or in more specific terms as reduced “reward delay” or as an attenuation of a “behavioural inhibition system”. In a recent publication we have described an experimental test in which decision making in the rat can be studied. The model is derived from ethology, in particular from optimal foraging theory. In order to solve the task, the animal must choose correctly between two options. For each option the probability of its resulting in a reward (water) has to be estimated on the basis of available information and to be related to the cost of performing it. We found that diazepam, in a dose that did not significantly affect the ability to perform the options per se, caused a strong impairment when these options, on the basis of available information, had to be combined into functional sequences in a decision making procedure. The results obtained cannot be explained on the basis of disinhibition or response perseveration. The hypothesis is advanced that benzodiazepines alter decision making in a more nonspecific may, by, for example, affecting the evaluation of the learned significance of stimuli in the environment.
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  • 93
    ISSN: 1432-2072
    Keywords: Place preference ; Heroin ; β-endorphin ; Naloxone ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of β-endorphin as a possible mediator in the reinforcing properties of opiates was investigated using a conditioned place preference paradigm. Heroin, a synthetic opiate known to have reinforcing properties, produced a strong preference for an environment previously paired with heroin injection at all doses tested (0.25, 0.5, 1.0, 2.0 mg/kg SC). No such place preference was observed following saline injections. Rats also showed dose-dependent place preference for the environment paired with β-endorphin when injected intracerebroventricularly (significant dose was 2.5 μg). At higher doses (5.0 and 10.0 μg) rats showed no preference for the paired environment, but were catatonic. Pretreatment with naloxone (0.04, 0.2, 1.0 mg/kg SC) attenuated the rewarding effect of β-endorphin (2.5 μg) at all doses tested. The lowest dose of naloxone which had no aversive effect when tested alone could also significantly block the positive effect of β-endorphin. The reinforcing dose of β-endorphin (2.5 μg) also produced an increase in locomotor activity, when tested in photocell cages. This suggests that the hyperactivity induced by β-endorphin may contribute to the preference for an environment previously paired with the same drug. The reinforcing effect of β-endorphin is most probably mediated by the mu and/or delta opioid subtype receptor, since β-endorphin has a high affinity for these receptors. These results demonstrate positive reinforcing properties of β-endorphin in the central nervous system.
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  • 94
    ISSN: 1432-2072
    Keywords: DRL ; Chlordiazepoxide ; Naloxone ; Benzodiazepines ; Opiates ; Learning ; Nonreward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The opiate antagonist naloxone can completely or partially reverse the effects of the benzodiazepines on appetitive behaviours and conflict tasks involving electric shook. If naloxone changes the anxiolytic action of the benzodiazepines it should, theoretically, be effective in tasks employing nonreward as well as those employing shock. We tested naloxone and chlordiazepoxide on acquisition and performance of a nonreward task, DRL. With both continuous administration during acquisition of DRL, and intermittent administration during stable performance, chlordiazepoxide (5 mg/kg IP) increased burst responding and shifted the peak of the inter-response time (IRT) distribution curve to shorter IRTs. Naloxone (3 mg/kg IP) blocked the effects of chlordiazepoxide on acquisition of DRL. Naloxone (3 mg/kg and 10 mg/kg IP) did not change the effects of chlordiazepoxide on well-learned performance of the DRL schedule. These results show that endogenous opiates could mediate some but not all of the actions of the benzodiazepines. They also suggest that state-dependent and “truly anxiolytic” effects of the benzodiazepines (McNaughton 1985) may have different pharmacological substrates.
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  • 95
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    Psychopharmacology 91 (1987), S. 139-146 
    ISSN: 1432-2072
    Keywords: Autoreceptors ; Bromocriptine ; CQ 32-084 ; Dopamine ; Exploratory behaviour ; Mesulergine ; Multivariate statistics ; Pergolide ; 3-PPP ; Rat ; Sulpiride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of six putative dopamine receptor agonists on exploratory behaviour in rats were assessed: pergolide, (+)- and (-)-3-PPP, bromocriptine, mesulergine and CQ 32-084. Behaviour was automatically recorded in a holeboard apparatus and the data were analysed by the novel multivariate statistical method of partial least squares. All six substances suppressed exploratory behaviour at low doses. Pergolide and (+)-3-PPP-induced stereotyped behaviour at higher doses. The suppression of exploration induced by pergolide was completely antagonised by sulpiride, partly antagonised by metoclopramide and weakly affected by haloperidol pretreatment. The effects of a low dose of (+)-3-PPP, bromocriptine or CQ 32-084, but not (-)-3-PPP or mesulergine, were antagonised by sulpiride. These findings support the hypotheses that pergolide, (+)-3-PPP, bromocriptine and CQ 32-084 inhibit exploration via stimulation of dopamine receptors. The present data do not substantiate the hypothesis that the suppression of exploration induced by (-)-3-PPP is mediated by stimulation of dopamine autoreceptors. A detailed analysis of the dose response curves for pergolide and (+)-3-PPP indicates that the latter compound may have effects in addition to those of a dopamine receptor agonist.
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  • 96
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    Psychopharmacology 92 (1987), S. 313-319 
    ISSN: 1432-2072
    Keywords: Pentylenetetrazol ; Morphine ; Fentanyl ; U 69 593 ; Mr 2034 ; Bremazocine ; Phencyclidine ; Drug discrimination ; Anxiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to detect the stimulus properties of pentylenetetrazol (PTZ), 16 mg/kg, and prototypic drugs for mu, kappa and sigma opioid receptors were tested for their ability to block or substitute for PTZ. Only the sigma agonist, phencyclidine, showed any capacity for blocking the PTZ stimulus. Drugs with selective kappa or sigma actions did not substitute for PTZ. However, morphine, fentanyl and Mr 2034 did substitute for the PTZ stimulus. This substitution was found to be centrally mediated in that quaternary morphine did not produce a PTZ-like stimulus. In contrast to the substitution of these drugs for PTZ, in rats trained to detect the stimulus properties of fentanyl, no substitution of PTZ for the fentanyl stimulus occurred. In tests of the capacity of various drugs to block the PTZ-like stimulus of mu agonists, the stimulus produced by morphine or fentanyl was blocked by naloxone, diazepam and haloperidol, but not by scopolamine. These results demonstrate that drugs with mu agonist properties show a one-way substitution for the discriminative stimulus produced by PTZ. The observation that haloperidol blocked the PTZ-like stimulus of mu agonists suggests the possible involvement of dopaminergic mechanisms in the mediation of the effect.
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  • 97
    ISSN: 1432-2072
    Keywords: Antidepressants ; Ergometrine ; Neuroleptics ; Nucleus accumbens ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study assesses the behavioural significance of the (-)sulpiride binding sites in the rat nucleus accumbens that bind antidepressants with high affinity and neuroleptics with low affinity. The effects were measured by intra-accumbens injections of typical and atypical antidepressants or neuroleptics, either given alone or in combination with ergometrine (1 μg/0.5 μl per side) on rat locomotor activity in a familiar environment. In addition, the after-effects of the combined ergometrine-drug treatment upon locomotor activity were analyzed. The antidepressants shared a common profile of effects. Thus, none of the antidepressants significantly altered locomotor activity in naive rats. Moreover, each antidepressant produced after-effects which were similar to those elicited in the acute ergometrine experiments. However, some antidepressants (amitriptyline and zimelidine) potentiated the ergometrine response, while other antidepressants (desipramine, mianserin and clorgyline) attenuated this response. (-)Sulpiride (0.5 μg) decreased the ergometrine response when given together with ergometrine or 48 h earlier. Haloperidol had to be given in a dose that was 20 times higher than that of (-)sulpiride in order to be effective. Clozapine (1–10 μg) failed to alter the ergometrine response when given together with ergometrine. Only (-)sulpiride produced a dose-dependent attenuation of locomotor activity in naive rats. The present data are discussed in terms of the hypothesis that drugs with antidepressive effects mediate their behavioural effects via mesolimbic (-)sulpiride binding sites.
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  • 98
    ISSN: 1432-2072
    Keywords: Noradrenaline ; Dorsal noradrenergic bundle ; 6-Hydroxydopamine ; Operant behaviour ; Herrnstein's equation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible role of the dorsal noradrenergic bundle (DNAB) in the maintenance of operant behaviour by positive reinforcement was examined using a quantitative behavioural paradigm based on Herrnstein's (1970) equation which defines a hyperbolic relationship between steady-state response rate and reinforcement frequency in variable-interval schedules. Twelve rats received bilateral injections of 6-hydroxydopamine (4 μg/2 μl) into the DNAB; ten rats received sham injections. The rats were trained to steady state in a series of six variable-interval schedules of sucrose reinforcement affording reinforcement frequencies of 8–350 reinforcers per hour. Herrnstein's equation was fitted to the data obtained from each rat and to the averaged data obtained from the two groups. The values of both R max (the parameter of the equation expressing the theoretical maximum response rate) and K H (the parameter expressing the reinforcement frequency needed to maintain the half-maximal response rate) were significantly higher in the DNAB-lesioned group than in the sham-lesioned group. At the end of the behavioural experiment the rats were sacrificed for determination of catecholamine levels in the brain by high-performance liquid chromatography. The levels of noradrenaline in the neocortex and hippocampus of the DNAB-lesioned rats were approximately 10% of those of the sham-lesioned rats. The results indicate that destruction of the DNAB reduced the “value” of the reinforcer without impairing the animals' capacity to respond.
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  • 99
    ISSN: 1432-2072
    Keywords: Amphetamine-conditioned excitation ; Neuroleptic drugs ; Clonidine ; Lithium ; Animal model ; Mania ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats with a history of daily (21 days) amphetamine (2.5 mg/kg) treatment showed enhanced activity when under placebo in their amphetamine-associated environment. We found that this conditioned effect was reduced by haloperidol (0.06; 0.125; 0.25 mg/kg), pimozide (0.25; 0.5 mg/kg) and sulpiride (8; 16; 32 mg/kg) but only at doses similar to or, in the case of pimozide, higher than those required to antagonize the unconditioned stimulant effects of amphetamine (2.5 mg/kg). Conversely, we observed that clonidine (7; 15; 30; 60 μg/kg) or lithium regimen (between days 15 and 21) leading to lithium plasma levels of 1.3±0.1 mEq/1, abolished amphetamine-conditioned hyperactivity but did not affect the unconditioned stimulation of amphetamine or locomotor activity in control rats. Moreover, we found that hyperactivity induced by the daily anticipation of food delivery shared identical pharmacological sensitivity with the behavioural excitation produced by a conditioning history with amphetamine. In light of the antimanic properties of lithium and clonidine and the ability of this latter drug to reduce noradrenergic transmission, our findings raise the posibility that incentive activity may model noradrenergic-dependent aspects of mania.
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    Urological research 15 (1987), S. 303-306 
    ISSN: 1434-0879
    Keywords: Testicular torsion ; Rat ; Hemodynamics ; Hemorrhagic infarction ; Radiolabelled microspheres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experimental testicular torsion must be used for certain studies of clinical relevance, but most experimental models either do not provide hemodynamic alteration comparable to the clinical situation or cannot guarantee reproducibility. Using a rat model arterial perfusion and hemorrhagic infarction were correlated to the degree of both intra- and extravaginal testicular torsion. Arterial inflow was measured sequentially with radiolabelled microspheres, hemorrhagic infarction was judged by the increase of testicular weight. Maximal hemorrhagic infarction and reproducible values were found when the spermatic cord was twisted togehter with the tunica vaginalis for 360°–540°.
    Type of Medium: Electronic Resource
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