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  • 1985-1989  (866)
  • 1980-1984  (617)
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  • 101
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 99 (1989), S. 98-102 
    ISSN: 1432-2072
    Keywords: Sucrose preference ; Two-bottle test ; Dopamine ; Sulpiride ; SCH-23390 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of the dopamine D2 receptor antagonist sulpiride and the D1 antagonist SCH-23390 were examined, in rats, in two-bottle preference tests (sucrose versus water) and in single-bottle tests, at different sucrose concentrations. Both drugs decreased sucrose intake in single bottle tests, at low sucrose concentrations, but had no effect at high concentrations; reducing drive level had exactly the opposite pattern of effects. In two-bottle tests, both drugs reduced preference for the weakest sucrose concetration (0.7%) but increased preference for the strongest concentration (34%). The effects of antagonizing either subtype of DA receptor appear to be similar to those of reducing the concentration of sucrose.
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  • 102
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 99 (1989), S. 316-321 
    ISSN: 1432-2072
    Keywords: Aging ; Phosphatidylserine ; Spatial memory ; Passive avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Learning/memory deficits in senescent animals are widely used as a tool to evaluate the therapeutic potential of agents for treatment of age-associated cognitive dysfunction. As assessed in the Morris water maze test, aged (21–24 months) rats showed a variable loss of spatial memory. Aged non-impaired rats performed as well as young subjects, while aged impaired rats exhibited a severe and persistent place-navigation, deficit. Passive avoidance retention was similarly affected in the two aged subpopulations. Chronic oral administration of phosphatidylserine (50 mg/kg/day for up to 12 weeks), a pharmacologically active phospholipid, was found to improve both the spatial memory and the passive avoidance retention of aged impaired rats. Results are discussed with reference to the phosphatidylserine-induced improvement of age-associated deterioration of brain functions in rats.
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  • 103
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 99 (1989), S. 299-303 
    ISSN: 1432-2072
    Keywords: Enkephalin analogues ; Intranigral infusions ; Dyskinetic biting ; Tardive dyskinesia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leu- and Metenkephalin (Lenk and Menk) and their more stable analogues d-Ala-Leu- and d-Ala-Meten-kephalin (DALenk and DAMenk) as well as d-ala-d-Leu-and d-Ala-d-Metenkephalin (DADLenk and DADMenk) were infused bilaterally into substantia nigra in awake rats and oral movements were recorded for 90 min. DADLenk and DADMenk elicited dose-dependent biting dyskinesias with a chewing rate of about 90 jaw movements/min. DALenk produced a similar but weaker effect, whereas DAMenk, Lenk and Menk were ineffective in the doses given. These findings suggest a possible enkephalinergic mechanism underlying neuroleptic-induced tardive dyskinesias.
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  • 104
    ISSN: 1435-604X
    Keywords: Brain tumour ; Rat ; Detection ; Fluorescence ; Laser ; Haematoporphyrin derivative
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Physics , Technology
    Notes: Abstract Laser-induced fluorescence has been used for the identification of brain tumours in rats, which have been previously given tumour-seeking haematoporphyrin derivative. A pulsed nitrogen laser (λ=337 nm) was used in conjunction with an optical multichannel analyzer. For both inoculated RG-2 and TCVC rat-brain-tumour models, the blue autofluorescence was strongly reduced in the tumour compared with normal brain tissue, and at the same time the characteristic red-drug signal increased. The contrast between tumour and normal tissue was strongly enhanced by forming the ratio between the two signals. Implications for possible improvement of tumour delineation in brain tumour surgery are discussed.
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  • 105
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 115 (1989), S. 47-52 
    ISSN: 1432-1335
    Keywords: Alkylation ; Alkyl guanines ; Pancreas DNA ; Nitrosamines ; Acinar cells ; Duct cells ; Hamster ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activation of 3H-labeled N-nitrosobis(2-oxopropyl)amine ([3H]BOP) by pancreas acinar and duct tissue from Syrian hamsters and MRC-Wistar rats in vitro was measured as DNA alkylation. Hamster tissue was incubated with [3H]BOP (0.1 mM; 20 μCi/ml) for 2 h. Initial levels of alkylation were similar, 41.7±3.7 (acinar) and 51.5±7.8 (duct) dpm/μg DNA. Alkylation persisted for longer in duct (t/2〉46 h) than in acinar tissue (t/2=6 h). The faster repair of alkylation in acinar tissue was not due to acinar cell death. In rat duct tissue the level of alkylation 2 h after incubation (38.9±4.5 dpm/μg DNA) was similar to that in hamster ducts but declined more rapidly (t/2=27 h). Hamster and rat acinar and duct tissue was incubated with BOP followed by [3H]thymidine to measure DNA synthesis. BOP stimulated DNA synthesis in hamster but not in rat duct tissue or hamster acinar tissue. These data support the hypothesis that the duct tissue is the target tissue for BOP in Syrian hamsters.
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  • 106
    ISSN: 1432-2013
    Keywords: Phosphaturia ; Parathyroid hormone ; 25 Hydroxy-vitamin D3 ; Trifluoperazine ; Adenylate cyclase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous work from this laboratory has demonstrated that 25(OH) vitamin D3 [25(OH)D3] acutely suppresses the phosphaturic action of parathyroid hormone (PTH) and interferes with the PTH-induced activation of adenylate cyclase (AC). Calmodulin inhibitors block vitamin D-induced Ca2+ transport in the gut and phosphorus uptake in renal BBMV's. We have examined whether calmodulin antagonists affect the renal action of 25(OH)D3. Acute clearance experiments were performed in PTH-infused parathyroidectomized rats receiving 25(OH)D3 after pretreatment with trifluoperazine (TFP) or promethazine (P). In vitro PTH-induced activation of renal AC was also studied in membrane preparations from pretreated rats in the presence of 25(OH)D3. 25(OH)D3 reduced the PTH-stimulated increase in fractional excretion of phosphorus (CP/CIn) from 0.292±0.024 to 0.195±0.018 (p〈0.005) and urinary cAMP from 149.3±20.3 to 78.1±10.4 pmol/min (p〈0.01) and also blunted AC activation in vitro. TFP but not P abolished the effects of 25(OH)D3 both in vivo and in vitro. R 24571 also abolished the in vitro effect of 25(OH)D3. Thus, (1) TFP abolishes both the antiphosphaturic and the AC/cAMP-related actions of 25(OH)D3, (2) P does not have these effects, and (3) R 24571 abolishes the in vitro effect of 25(OH)D3. These results suggest that the antiphosphaturic effect of 25(OH)D3 acting via the AC/cAMP system may be calmodulin dependent.
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  • 107
    ISSN: 1435-2451
    Keywords: Portocaval shunt ; Liver cirrhosis ; Rat ; Lethality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im Lebercirrhose-Modell der Ratte hat die portocavale Anastomose eine sehr hohe Letalitet (87%). Durch eine präoperative Vorbereitung mittels einer Therapie, die einen eta blierten Stellenwert in der Behandlung der portosy stemischen Encephalopathie hat, wird erstmals experimentell eine Senkung der Operationsletalität dokumentiert, was den konsequenten klinischen Einsatz nahelegt.
    Notes: Summarry Following portocaval anastomosis a high lethality (87%) can be observed in a standardized micronodular liver cirrhosis model. By a special preoperative regimen this lethality can be reduced to 10%.
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  • 108
    ISSN: 1433-8580
    Keywords: Rat ; Liver cirrhosis ; Hypoxia ; Redox state ; Mitochondrial oxidative phosphorylative activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of hypoxia on hepatic mitochondrial function and energy status was studied in normal and carbon tetrachloride (CCl4)-induced cirrhotic rats. Under hypoxemia of 50 mm Hg-PaO2, hepatic energy status was suppressed both in normal and cirrhotic rats. After the reversal of hypoxia, it was completely restored in normal rats concomitant with a rapid elevation of hepatic mitochondrial redox state (overshoot phenomenon) and increase in the mitochondrial oxidative phosphorylative activity. By contrast, in cirrhotic rats, such an enhancement of mitochondrial function was not observed. It was clarified that cirrhotic liver mitochondria have little capacity to respond to the hypoxic stress. A lower resistance to hypoxic episode in cirrhotics might be attributable to the absence of mitochondrial enhancement which is a compensatory mechanism for the deranged energy metabolism of the liver.
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  • 109
    Electronic Resource
    Electronic Resource
    Springer
    Research in experimental medicine 189 (1989), S. 321-329 
    ISSN: 1433-8580
    Keywords: Fibronectin ; Nerve fibrosis ; Fibrin adhesives ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Although the fibrin adhesion enjoys increasing success in many areas of surgery, it has not, however, become fully established in nerve anastomosis. It was in this area particularly that significant advantages were expected, especially by the avoidance of suture granulomas. As the fibrin clot dissolved prematurely, however, and dehiscences ensued, antifibrinolytic substances had to be added to the adhesive. Fibroses occurred frequently as a result, which to date encumber nerve adhesive. We examined fibronectin for its fibrosis-inducing effect, comparing both presently available fibrin adhesive systems, because one contained up to 5 times more fibronectin per milliliter than the other. On the basis of a test grouping using 100 and 1000 KIU aprotinin/ml, we were able to establish that fibronectin in fibrin adhesives possesses a fibrosis-promoting effect.
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  • 110
    Electronic Resource
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    Springer
    Research in experimental medicine 189 (1989), S. 281-287 
    ISSN: 1433-8580
    Keywords: Serotonin ; Tryptophan ; Small intestine ; Rat ; Pargyline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the release of serotonin from intestinal enterochromaffin cells, we used an in vitro technique which allows studies excluding overlapping influences from outside the gut. The entire small intestine of rats fed a standard or tryptophan-enriched (3% of total) diet was totally isolated by ligatures with the exception of the superior mesentric artery and portal vein that supply and drain the intestine. Simultaneously to the vascular perfusion (Krebs-Ringer bicarbonate buffer, 0,4% human albumin, 5 mM glucose, 0.6 mM glutamine) the gut lumen was infused (buffer or 0.1 N HCL). Acidification of the gut lumen resulted in an increment of venously released tryptophan and serotonin. After feeding tryptophan-enriched food the release of tryptophan was increased. However, the total amount of released serotonin after tryptophan diet did not differ as compared to that after standard diet. Addition of a monoamino-oxidase inhibitor (pargyline) to the arterial perfusate enhanced the released amount of serotonin 3-fold in the portal venous effluent (at a concentration of 1 mM but not 0.1 mM). Recovery studies done by arterial infusions of serotonin (1 µM, 10µM) and evaluation of the amounts venously released revealed a high loss of infused serotonin (40%–70%). Our data suggest gut-born serotonin to more likely play a paracrine role than a role as a classical hormone.
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  • 111
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    European journal of applied physiology 58 (1989), S. 446-451 
    ISSN: 1439-6327
    Keywords: Rectal temperature ; Tail vasomotor response ; Exercise ; Estrus cycle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In female rats, rectal temperature (T re), tail vasomotor response, oxygen uptake $$\left( {\dot V_{{\text{O}}_{\text{2}} } } \right)$$ , and carbon dioxide production $$\left( {\dot V_{{\text{CO}}_{\text{2}} } } \right)$$ were measured in proestrus and estrus stages during treadmill running at two different speeds at an ambient temperature (T a) of 24° C. Experiments were performed at 2.00–6.00 a.m., when the difference inT re was greatest between the two stages;T re at rest in the estrus stage was 0.54° C higher than in the proestrus stage. In a mild warm environment, thresholdT re for a rise in tail skin temperature (T tail) was also higher in the estrus stage than in the proestrus stage. In contrast, no difference was seen in the thresholdT re and steady stateT re at the end of exercise between proestrus and estrus stages. These values were higher at the higher work intensity. $$\dot V_{{\text{O}}_{\text{2}} } $$ was also similar between the two stages, except in the second 5 min after the beginning of exercise, when $$\dot V_{{\text{O}}_{\text{2}} } $$ was greater andT re rose more steeply in the proestrus stage. These data indicate that deep body temperature during exercise is regulated at a certain level depending on the work intensity and is not influenced by the estrus cycle.
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  • 112
    Electronic Resource
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    Cell & tissue research 256 (1989), S. 303-307 
    ISSN: 1432-0878
    Keywords: Arachnoid cells ; Tight and gap junctions ; Cold injury ; Ultrastructure ; Freeze-fracture technique ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The junctional complexes of cells in the outer arachnoid layer overlying the cerebral cortex of 2-week-old rats were examined with freeze-fracture electron microscopy up to 60 min after transcranial cold injury to the dorsal surface of the brain. Within 30 min after injury, areas of gap and tight junctions with morphological features characteristic of junction formation and/or junction disruption were found scattered among normal junctional complexes in some arachnoid cells. Within 60 min after injury, tight junctions with features typical of less leaky zonulae occludentes were present in all arachnoid cells examined. These morphological features include increases in the number of tight junctional strands and the number of strand-to-strand anatomoses. Gap junctions were interspersed among the tight junctional strands, and many were completely encircled by the strands. The increase in the number and complexity of the tight junctional strands in response to brain injury may be the morphological basis for the maintenance of the cerebrospinal fluid-blood dural barrier.
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  • 113
    ISSN: 1432-0878
    Keywords: SEM ; TEM ; Interstitial cell ; Myenteric plexus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An extensive cellular network becomes visible over the myenteric plexus of the rat after removal of the overlying tissues under the scanning electron microscope. The cells are mainly stellate and have many slender processes via which they interconnect. They form a three-dimensional network and are closely associated with the ganglia and nerve bundles, and also extend over the smooth muscle cells. They are considered to correspond to the interstitial cells of Cajal because of their peculiar arrangement and their topography. Transmission electron-microscopic evidence demonstrates that the majority of those cells have features of fibroblasts. Gap junctions and intermediate junctions are observed between these fibroblast-like cells, and also between them and smooth muscle cells. Examination of serial thin sections reveals that single fibroblast-like interstitial cells connect to both circular and longitudinal muscle cells via gap junctions. It is suggested that the network of interstitial cells conducts electrical signals.
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  • 114
    ISSN: 1432-0878
    Keywords: Adrenal medullary endothelial cells ; Pheochromocytoma (PC12) cells ; Co-culture ; Cell surface extracts ; Adhesion ; Cell-cell interactions ; Bovine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Chromaffin cells in the adrenal medulla are found in close proximity to capillary endothelial cells, thereby forming the classical endocrine complex. To examine the possible chemical basis of their interaction in more detail, we have grown bovine adrenal medullary endothelial (BAME) cells in monolayer cultures and added to them pheochromocytoma (PC12) cells, a chromaffin tumor cell line of rats. The PC12 cells were chosen because of the similarities they share with adrenal medullary chromaffin cells. PC12 cells rapidly attached to BAME cells cultures, their rate of adhesion being significantly enhanced over binding of PC12 cells to either uncoated plates or to monolayers of unrelated cell cultures. Consistent with this observation, we noted that the extracellular matrix (ECM) derived from the BAME cells did not enhance PC12 cell adhesion and did not promote neurite sprouting as previously described for ECM derived from corneal endothelial cells. The specific adhesion between PC12 and BAME cells could be abolished by cell surface extracts derived from these two cells but not by extracts derived from unrelated cell types. This activity was heat-labile, sensitive to trypsin and, to a lesser extent, to neuraminidase. We therefore conclude that PC12 cells may interact with BAME cells by specific proteinaceous adhesive factors associated with their plasma membranes. These interactions might represent the formative role of cell-cell contacts in the organization of the developing adrenal gland.
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  • 115
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    Journal of comparative physiology 159 (1989), S. 237-242 
    ISSN: 1432-136X
    Keywords: Amylase ; Mosquitofish ; Rat ; Drosophila ; Structure ; Function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Amylases from the mosquitofish (Gambusia affinis holbrooki, Pisces: Poeciliidae) and rat were purified and compared withDrosophila amylases in terms of structure and function. At the structural level, amino acid compositions of the three amylases were compared. At the functional level, amylase activities were compared on various substrates and in the presence of inhibitors. While the amylases from all three organisms had properties typical of alpha-amylases, both structural and functional differences were observed. Using resemblance coefficients of distance and similarity from numerical taxonomy, it was determined that the amylases from the rat andDrosophila were more similar to each other than either was to amylase from the mosquitofish, and that structural differences between the amylases did not reflect functional differences, i.e. there was no correlation between amylase structural and functional distances.
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  • 116
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    Cell & tissue research 256 (1989), S. 553-558 
    ISSN: 1432-0878
    Keywords: Transforming growth factor (TGF)-β ; Myocardium ; mRNA ; Fibroblast ; Cardiomyocyte ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Transforming growth factor-β (TGF-β) is a biologically active polypeptide present in normal tissues as well as transformed cells. Two structurally related forms of this peptide are TGF-β 1 and TGF-β 2. Using freshly isolated cardiomyocytes and non-myocyte heart cells, and a [32P]-labelled cDNA probe to human TGF-β 1, we demonstrated that mRNA for TGF-β 1 could be detected only in the nonmyocyte fraction of heart cells. In the present study, the distribution of TGF-β 1 in the heart was determined by immunofluorescence staining by use of a polyclonal antibody to porcine TGF-β 1 in cryostat sections of rat heart. Immunofluorescence staining was intense around the blood vessels and radially diffuse in the surrounding myocardium.
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  • 117
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    Cell & tissue research 256 (1989), S. 559-565 
    ISSN: 1432-0878
    Keywords: Retrograde tracing ; Immunocytochemistry ; Vascular innervation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The origin of nerve fibers to the superficial temporal artery of the rat was studied by retrograde tracing with the fluorescent dye True Blue (TB). Application of TB to the rat superficial temporal artery labeled perikarya in the superior cervical ganglion, the otic ganglion, the sphenopalatine ganglion, the jugular-nodose ganglionic complex, and the trigeminal ganglion. The labeled perikarya were located in ipsilateral ganglia; a few neuronal somata were, in addition, seen in contralateral ganglia. Judging from the number of labeled nerve cell bodies the majority of fibers contributing to the perivascular innervation originate from the superior cervical, sphenopalatine and trigeminal ganglia. A moderate labeling was seen in the otic ganglion, whereas only few perikarya were labeled in the jugular-nodose ganglionic complex. Furthermore, TB-labeled perikarya were examined for the presence of neuropeptides. In the superior cervical ganglion, all TB-labeled nerve cell bodies contained neuropeptide Y. In the sphenopalatine and otic ganglia, the majority of the labeled perikarya were endowed with vasoactive intestinal polypeptide. In the trigeminal ganglion, the majority of the TB-labeled nerve cell bodies displayed calcitonin gene-related peptide, while a small population of the TB-labeled neuronal elements contained, in addition, substance P. In conclusion, these findings indicate that the majority of peptide-containing nerve fibers to the superficial temporal artery originate in ipsilateral cranial ganglia; a few fibers, however, may originate in contralateral ganglia.
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  • 118
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    Cell & tissue research 256 (1989), S. 447-456 
    ISSN: 1432-0878
    Keywords: MAP2 ; Actin ; Dendritic spines ; Spine apparatus ; Spine synapses ; Postsynaptic density ; Synaptic plasticity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of MAP2 and actin in dendritic spines of the visual and cerebellar cortices, dentate fascia, and hippocampus was determined by using immunogold electron microscopy. By this approach, we have confirmed the presence of MAP2 in dendritic spines and identified substructures within the spine compartment showing MAP2 immunoreactivity. MAP2 immunolabeling was mainly associated with filaments which reacted with a monoclonal anti-actin antibody. Also, by immunogold double-labeling we colocalized MAP2 with actin on the endomembranes of the spine apparatus, smooth endoplasmic reticulum, and in the postsynaptic density. Labeling was nearly absent in axons and axonal terminals. These results indicate that MAP2 is an actin-associated protein in dendritic spines. Thus, MAP2 may organize actin filaments in the spine and endow the actin network of the spine with dynamic properties that are necessary for synaptic plasticity.
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  • 119
    ISSN: 1432-0878
    Keywords: Gastrin ; Gastrin-releasing peptide ; Bombesin ; Stomach ; Autonomic innervation ; Immunohistochemistry ; Guinea pig ; Rat ; Dog ; Man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The relationship between bombesin-like immunoreactive (bombesin-LI) nerve fibres and gastrin-LI G-cells was examined in gastric antral mucosa from guineapig, rat, dog and man using a double-labelling fluorescence immunohistochemical technique. The greatest density of bombesin-LI nerve fibres was found within the basal mucosa in all species and the density of innervation decreased towards the luminal surface. Most G-cells were in a band occupying approximately the middle third of the mucosa. The proportion of G-cells found within a distance of 2 μm from bombesin-LI nerve fibres was low in all species (6% in the guinea-pig, 22% in the rat, 14% in the dog, and 9% in the human). It is proposed that the neuropeptide released from bombesin-LI antral mucosal nerve fibres traverses distances of greater than several μm to reach the target G-cells. This may be achieved by passage through the mucosal microcirculation.
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  • 120
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    Cell & tissue research 257 (1989), S. 263-268 
    ISSN: 1432-0878
    Keywords: Retinol ; Vacuoles ; Immunohistochemistry ; Plasma proteins ; Hepatocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The vacuoles occurring in rat hepatocytes after intraportal injection of retinol (33 or 67 μg) were examined immunohistochemically using respective antibodies against rat albumin, human retinol-binding protein, human ceruloplasmin, human α 1-antitrypsin, human transferrin, and human prealbumin as representative plasma proteins. The occurrence of the vacuoles reached a numerical maximum 30 min after injection of 67 μg retinol, followed by a temporal decrease. Hepatocytes from control rats, which had been intraportally injected with either blood plasma diluted to 2/3 concentration or with retinol palmitate solvent (castor oil) dissolved in blood plasma, showed immunoreactive fine granules without the occurrence of vacuoles in the cytoplasm. Identical vacuoles in serial sections appeared immunohistochemically either immunoreactive or non-immunoreactive for all the antibodies used, with rare exceptions. The occurrence of several rare exceptions suggested that 2 kinds of vacuoles might be formed in different cytoplasmic compartments. A zonal distribution of vacuoles was apparent in the hepatic laminae (or acini) within the liver lobules. The vacuoles were predominantly distributed in zone 2, and to a lesser extent in zone 3 and zone 1 in that order.
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  • 121
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    Virchows Archiv 414 (1988), S. 77-81 
    ISSN: 1432-2307
    Keywords: Epithelium ; Intestine ; Desquamation ; Restitution ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ loops of large bowel of anaesthetised rats were used to observe epithelial restitution following surface desquamation using solutions of bile salts. The treatment induced complete surface desquamation but no disruption of the basal lamina. There was evidence of, cell migration at 30 min, and a complete surface epithelium two h post treatment. Neither a continuous contact between migrating cells and the basal lamina, nor a complete covering of secreted mucus, appeared necessary for epithelial restitution to occur.
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  • 122
    ISSN: 1432-2072
    Keywords: LY 171555 ; SKF 38393 ; Combined D1 and D2 stimulation ; SCH 23390 ; D1 supersensitivity ; Locomotor activity ; Grooming ; Stereotyped behaviour ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The selective D1 receptor stimulant SKF 38393 dose-dependently increased grooming time in rats without affecting locomotor activity or eliciting stereotyped behaviour. The selective D2 receptor agonist LY 171555 induced a dose-dependent increase in rat motility, a marked decrease in grooming time and a low occurrence of stereotyped behaviour. Concurrent administration of the two selective agonists induced high-degree stereotyped responses and reductions in locomotor and grooming behaviours. Rats withdrawn from repeated treatment with the selective D1 receptor blocker SCH 23390 (0.05 mg/kg twice daily for 21 days; 7 days of washout) did not exhibit any change of locomotor and grooming responses to threshold doses of LY 171555 and SKF 38393 given alone or in combination. On the contrary, a significantly greater occurrence of high-degree stereotyped responses to the combination of the two selective agonists was observed. The data support the view that D1 and D2 receptors have a cooperative role in the generation of stereotypies and suggest that D1 receptor supersensitivity needs D2 stimulation to be revealed.
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  • 123
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    Psychopharmacology 95 (1988), S. 413-417 
    ISSN: 1432-2072
    Keywords: DRL-schedule ; Imipramine ; Mianserin ; Idazoxan ; Yohimbine ; Amphetamine ; α2-Adrenoceptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have reported that antidepressant drugs exert specific effects on responding maintained by DRL schedules of reinforcement, giving rise to increased frequencies of reinforcement. In order to investigate whether the α2-adrenoceptor antagonist idazoxan would produce similar effects, the actions of this compound were compared with those of yohimbine, imipramine, mianserin and d-amphetamine in rats trained to lever press for food reinforcement on a DRL 60-s schedule. Neither imipramine nor mianserin produced any effects on response rate or reinforcement frequency, except at the highest doses. In contrast, both idazoxan and yohimbine gave rise to dose-related increases in rates of responding and consequent decreases in reinforcement frequencies. Amphetamine also increased responding, but higher doses of this drug produced marked hyperactivity and stereotyped movements which were not observed after idazoxan and yohimbine. Although the present behavioural baseline was not sensitive to antidepressants, it demonstrated an unexpected activity of two α2-adrenoceptor antagonists which deserves further investigation.
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  • 124
    ISSN: 1432-2072
    Keywords: Anhedonia ; Drive ; Extinction ; Free feeding ; Neuroleptic ; Pimozide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Both pimozide pretreatment and free feeding caused within-session and between-session decrements in variable interval operant performance; response decrements generated under pimozide were maintained on transfer to free feeding, and vice versa. On subsequently testing under extinction conditions (after food deprivation and drug free) large initial increases in responding were seen in all groups, and subsequent response decrements in extinction were steeper than in either pimozide or free feeding conditions. The effects of pimozide pretreatment do not resemble those of extinction, but may in some circumstances be functionally equivalent to a decrease in drive level.
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  • 125
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    Keywords: Amphetamine ; Circling behavior ; Asymmetry ; Pavlovian conditioning ; Sensitization ; Placebo ; Latent inhibition ; Extinction ; Reverse tolerance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amphetamine-induced circling behavior increases over the course of repeated administration of the drug; likewise, after repeated administration of amphetamine, an injection of saline prior to placement of the rat in the test apparatus previously associated with the pharmacologic effects of amphetamine will increase circling behavior. Experiments were designed to determine if either of these effects would respond to manipulation of the temporal contiguity between the test environment and the peak effects of amphetamine. The placebo-like response, in accordance with a Pavlovian conditioned response, was reduced by prior non-reinforced exposure to the test environment and subject to extinction. In contrast, the increase in the amphetamine-induced response was entirely dependent on the test environment but not affected by latent inhibition or extinction. These and previous findings indicate that the development and expression of the placebo-like response is the result of a Pavlovian associative process. Although amphetamine sensitization is environment dependent, it does not resemble a conditioned response in other respects.
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  • 126
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    Keywords: Tachykinins ; Senktide ; Cholinergic ; Autoreceptor ; 6-Hydroxydopamine ; Yawning ; Mouth movements ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The selective NK-3 tachykinin receptor agonist senktide elicited yawning, chewing mouth movements and sexual arousal following subcutaneous administration (0.1–1.0 mg/kg) in the rat. These responses were not significantly affected by the dopamine antagonist haloperidol (0.03 mg/kg) or by 6-hydroxydopamine lesions of the nigrostriatal projection. In contrast, the behaviours were markedly attenuated by the peripheral and central muscarinic antagonist scopolamine (1 mg/kg), but not by the peripheral muscarinic antagonist N-methylscopolamine (1 mg/kg). These findings suggest that stimulation of NK-3 receptors produces yawning, chewing and sexual arousal by directly activating central cholinergic neurons.
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  • 127
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    Keywords: 8-OH-DPAT ; Feeding ; Drinking ; Palatability ; Appetite ; Fenfluramine ; Satiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The 5-HT1A agonist 8-OH-DPAT, at a dose of 30 μg/kg, enhanced the consumption of sweetened wet mash and sweetened milk in non-deprived rats. In partially satiated rats, sensitivity to the hyperphagic effect of 8-OH-DPAT on wet mash intake was substantially increased, so that the minimally effective dose was reduced to 3 μg/kg. Similarly, 8-OH-DPAT was more efficacious in increasing milk intake in satiated rats. Thus, 30 and 40 μg/kg 8-OH-DPAT produced a 4-fold increase of milk intake in completely satiated rats compared to a 2-fold increase in partially satiated animals at a dose of 30 μg/kg. The increased intake of liquid and wet mash diets observed after treatment with low doses of 8-OH-DPAT argues against the involvement of non-specific gnawing in the increased consumption of solid food produced by the drug. Rather, the data suggest that 8-OH-DPAT may specifically stimulate appetite by counteracting a tonic serotonergic inhibition of feeding. The present experiments also showed that 8-OH-DPAT attenuates fenfluramine-induced anorexia which is thought to depend on increased serotonergic neurotransmission.
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  • 128
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    Psychopharmacology 94 (1988), S. 84-91 
    ISSN: 1432-2072
    Keywords: Serotonin ; 8-OH-DPAT ; Anxiety ; Stress ; Raphe nuclei ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of a selective serotonin1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were studied in two animal models of anxiety. Peripherally injected 8-OH-DPAT in doses ranging from 0.125 to 2.0 mg/kg did not increase black-white transitions (BWT) and black square entries (BSE) in a two-compartment exploratory test or punished responding in a test of conditioned suppression of drinking. With 2.0 mg/kg 8-OH-DPAT BSE and unpunished responding were reduced. In an investigation of the drinking time of water-deprived rats, naive or habituated to the test environment, 1.0 and 2.0 mg/kg 8-OH-DPAT increased the drinking time of naive rats but 2.0 mg/kg 8-OH-DPAT reduced that of habituated animals. In animals deprived of water for 48 h or subjected to immobilization stress for 2 h, 1.0 mg/kg 8-OH-DPAT increased BWT and BSE values in the two-compartment exploratory test. Infusions of 5 μg/0.5 μl 8-OH-DPAT in the nucleus raphe medianus increased BWT and BSE values in the exploratory test and punished responding in the test of conditioned suppression of drinking, whereas the same dose of 8-OH-DPAT injected in the nucleus raphe dorsalis had no effect on punished but suppressed unpunished responding. The effects of 8-OH-DPAT are only detectable in the appropriate experimental conditions. When injected systemically, the effects are evident when a state of arousal of the animals contributes to the overall behavioural output. 8-OH-DPAT shows effects comparable to those of established anxiolytics such as benzodiazepines and barbiturates when it is injected in the nucleus raphe medianus, but not in the dorsalis. The data support the hypothesis that brain serotonin is involved in the mechanisms mediating behavioural suppression in the presence of aversive stimuli.
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  • 129
    ISSN: 1432-2072
    Keywords: Amygdala ; Corticotropin releasing factor ; Exploration ; Memory modulation ; Open field ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of intra-amygdala injections of corticotropin-releasing factor (CRF) on memory and exploratory behavior in rats were examined in the present study. Rats with chronically implanted cannulae received intra-amygdala injections of vehicle or CRF at a dose of 0.01, 0.1 or 1.0 μg, either immediately after the inhibitory avoidance training or prior to the open field activity test. Results indicated that while CRF at low (0.01 μg) and high (1.0 μg) doses produced no significant effect on retention or exploration, immediate post-training intra-amygdala injections of CRF at the medium dose (0.1 μg) significantly improved retention of the inhibitory avoidance response. The same dose of CRF, given shortly prior to the open field activity test, decreased locomotor activity, rearing and hole-poke responses in rats. These results suggest that the amygdala is one of the anatomical loci involved in CRF modulation of memory processing and exploration in rats. The implication of CRF in mediating the influences of stress on behavior is discussed.
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  • 130
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    Psychopharmacology 96 (1988), S. 262-266 
    ISSN: 1432-2072
    Keywords: Alpha-melanotropin ; Inulin ; Blood-brain barrier ; Lipid solubility ; Pharmacokinetics ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The permeability of the blood-brain barrier (BBB) to immunoreactive alpha-melanotropin (α-MSH) was quantified in rats pretreated with monosodium l-glutamic acid to deplete their CNS stores of endogenous α-MSH. The methodology, suitable for poorly permeable substances, monitored blood and brain tissue concentrations of α-MSH over 15 min following intravenous injection of 30 nmol synthetic α-MSH. Rate constants for entry of α-MSH into brain tissue were estimated from separate nonlinear least-squares fits of connecting two- and one-compartment open models to plasma and extravascular brain tissue concentration data, respectively. Comparisons were made to rate constants measured similarly for 14C-inulin. The BBB had a low permeability to immunoreactive α-MSH, consistent with peptide penetrating the barrier by passive diffusion dependent upon the lipid solubility of the molecule.
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  • 131
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    Psychopharmacology 94 (1988), S. 133-137 
    ISSN: 1432-2072
    Keywords: Diazepam ; Haloperidol ; Domperidone ; 6-Hydroxydopamine ; DSP-4 ; Place conditioning ; Dopamine ; Noradrenaline ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The conditioned place preference paradigm was used to investigate the neurochemical and neuroanatomical substrates which mediate the rewarding properties of diazepam. The results confirmed that diazepam (1 and 2.5 mg/kg, IP) produced place preference for a distinctive environment that had previously been paired with injections of the drug. Pretreatment with haloperidol (0.1 mg/kg) antagonised the place preference induced by diazepam (1 mg/kg). Pretreatment with domperidone (2 mg/kg) failed to influence this effect of diazepam. Haloperidol (0.1 mg/kg) and domperidone (2 mg/kg) alone did not produce place aversion. In separate experiments the diazepam-induced place preference was examined in rats having 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens. These animals did not show preference for the compartment associated with diazepam. Depletion of central noradrenaline produced by systemic injections of DSP4 did not affect diazepam-induced place preference conditioning. These findings suggest that dopamine-containing neurons of the mesolimbic system are a component of the neural circuitry that mediates the reinforcing properties of diazepam.
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  • 132
    ISSN: 1432-2072
    Keywords: Noradrenaline ; DSP4 ; Operant behaviour ; Herrnstein's equation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of the selective noradrenaline neurotoxin DSP4 on steady-state operant behaviour 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. Eleven rats received injections of DSP4 (two doses of 50 mg/kg, intraperitoneally), and 12 rats received injections of the vehicle alone. The rats were trained to steady state in a series of six variable-interval schedules of sucrose reinforcement, affording scheduled reinforcement frequencies of 4–360 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 value ofK H (the parameter expressing the reinforcement frequency needed to maintain the half-maximal response rate) was higher in the DSP4-treated rats than in the control rats; the value ofR max (the parameter expressing the maximum response rate) did not differ significantly between the two groups. At the end of the behavioural experiment the rats were sacrificed for determination of the concentrations of catecholamines in the brain by high-performance liquid chromatography. The levels of noradrenaline in the parietal cortex, hippocampus and cerebellum of the DSP4-treated rats were less than 20% of those of the control rats. The results provide further evidence that central noradrenergic neurones are involved in the maintenance of operant behaviour by positive reinforcement.
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  • 133
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    Psychopharmacology 94 (1988), S. 545-550 
    ISSN: 1432-2072
    Keywords: Stress ; DMI ; Sucrose preference ; Microstructural analysis ; Apomorphine ; Eating time ; Eating rate ; Dopamine autoreceptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats exposed for 6 weeks to a variety of mild unpredictable stressors showed reduced consumption of a preferred sucrose solution. The deficit was apparent after 1 week of stress and was maintained for at least 2 weeks after termination of the stress regime. Sucrose preference was unaffected by 2 weeks of treatment with the tricyclic antidepressant DMI but returned to normal after 3 weeks of DMI treatment. Subsensitivity to the anorexic effect of a low dose of apomorphine was seen in vehicle-treated stressed animals, and in unstressed animals following withdrawal from DMI. In both cases, the changes resulted from a failure of apomorphine to reduce eating time (rather than from changes in eating rate); this effect is assumed to represent a subsensitive response to stimulation of dopamine cell body autoreceptors. As the same effect is seen in anhedonic stressed animals and in animals withdrawn from DMI, it is concluded that dopamine autoreceptor desensitization probably does not contribute to clinical improvement following chronic antidepressant treatment.
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  • 134
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    Psychopharmacology 96 (1988), S. 237-242 
    ISSN: 1432-2072
    Keywords: Methysergide ; Cyproheptadine ; Metergoline ; Ritanserin ; Food intake ; Satiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two series of experiments examined whether 5-hydroxytryptamine (5-HT) antagonists induce feeding in rats. In the first series of experiments separate groups of rats were injected with various doses of methysergide, cyproheptadine, metergoline or ritanserin prior to a 2 h period of access to a wet mash diet which induced vigorous feeding under control conditions. None of the antagonists increased food intake in this paradigm. Rather, at certain doses, methysergide, cyproheptadine and ritanserin induced slight decreases in food intake. Since 5-HT may be involved in controlling satiety, it may be that a more appropriate test of the efficacy of these compounds involves administering them to maximally satiated rats. Consequently, the effects of these drugs were investigated in groups of rats which had fed to satiety immediately prior to drug treatment. In this paradigm methysergide, metergoline and ritanserin, but not cyproheptadine, induced definite increases in food intake. It is suggested that this effect occurs via a dissipation of satiety signals, and that these results further support the hypothesis that 5-HT is involved in controlling satiety. The possibility that these antagonists act on peripheral 5-HT systems is discussed.
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  • 135
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    Psychopharmacology 96 (1988), S. 281-284 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Oral administration ; Transdermal administration ; Nicotine ; Cytisine ; Arecoline ; Mecamylamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a standard two-lever drug discrimination paradigm, rats were trained to discriminate nicotine 0.5 mg/kg PO from saline. Injections occurred 15 min before the session. Subjects reached the training criterion in a mean of 38 sessions. Nicotine PO, SC, and IP generated similar dose-effect curves (ED50=0.073 mg/kg PO, 0.076 mg/kg SC, 0.090 mg/kg IP); the dose-effect curve for transdermal (TD) administration fell approximately 1 log unit to the right (ED50=1.34 mg/kg). The percentage of rats choosing the nicotine-appropriate lever peaked at 15 min and gradually decreased to 50% or less by 180 min for nicotine PO and TD, a time-decay function similar to that previously shown for SC administration. The nicotinic cholinergic agonist cytisine (0.5–8.0 mg/kg) PO and TD produced up to 56% nicotine-appropriate responding, while the muscarinic cholinergic agonist arecoline (1.0–4.0 mg/kg) PO and TD produced only saline-appropriate responding. The nicotine cue did not generalize to the cholinergic antagonist mecamylamine (0.125–0.5 mg/kg) PO or TD; mecamylamine 0.5 mg/kg PO but not TD completely blocked the PO and TD nicotine cues. These results show that an approximately equal cue occurs with PO, IP, and SC administration, and that the TD cue is considerably weaker. The significance of the procedure as an animal analog of human transdermal nicotine intake is discussed.
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  • 136
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    Psychopharmacology 96 (1988), S. 311-316 
    ISSN: 1432-2072
    Keywords: Rat ; Neuroleptics ; Catalepsy ; Dopamine receptors ; Muscarinic receptors ; SCH23390 ; Pilocarpine ; Atropine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an attempt to understand the nature of the interactions between D1 and D2 dopamine subsystems as well as between dopamine and acetylcholine, catalepsy was assessed in rats following various drug treatments. The D1-specific antagonist SCH23390 (0.1 mg/kg) produced prompt, potent and brief (〈90 min) catalepsy with an ED50 of 0.105 mg (0.3 μmol)/kg. Conversely, fluphenazine (0.1 mg/kg), spiroperidol (0.1 mg/kg), and haloperidol (0.2 mg/kg) all had comparably potent but more slowly rising and prolonged (〉240 min) effects. The action of SCH23390 was synergistic with spiroperidol, inhibited by apomorphine or atropine, unaffected by mecamylamine, and markedly potentiated by pilocarpine. However, pilocarpine was unable to significantly potentiate the action of fluphenazine or spiroperidol. It is inferred that SCH23390 differs from the classical neuroleptics in its mechanism of cataleptogenicity, that there is a cholinergic link with the D1 dopamine system, and further, that there may be a difference in the nature or impact of the cholinergic interaction with the D1 and D2 dopamine systems.
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  • 137
    ISSN: 1432-2072
    Keywords: Enkephalin ; Ventral mesencephalon ; Investigatory behaviour ; Motor behaviour ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mesolimbic dopamine (DA) system, originating in the ventral tegmental area and projecting to limbic forebrain regions, plays a crucial role in mediating several important aspects of behaviour. Proximal to these DA neurons are enkephalin-containing nerve fibers. In an attempt to characterize the behavioural role of enkephalinergic transmission in the VTA, the present experiment examined in detail the investigatory and motor responses to microinfusion of d-ala-met-enkephalin (DALA), a long lasting analogue of enkephalin, into the ventral tegmental area (VTA). Injections into the substantia nigra (SN) and the hippocampus (HPC) were also performed as controls for site specificity. The behavioural apparatus consisted of an eight-hole box monitored by a video camera. Four doses of DALA were injected in the VTA (0.05, 0.1, 1 and 2.5 μg/μl bilaterally in 1 μl volume) and one dose in the SN and HPC (0.1 μg/μl bilaterally in 1 μl volume). The effect of DALA injections in the VTA was characterized by an inverted U-shape dose-effect curve. The low doses (0.05 and 0.1) induced an increase in the frequency of hole visits accompanied by a decrease in the mean duration of visits, whereas the highest doses induced a decrease in hole visit frequency. Low doses of DALA had no effect on strategy or organization of exploration, whereas the high doses produced decreased switching between holes. After low doses of DALA, locomotor activity at the periphery of the testing box was not significantly affected but locomotor activity in the centre was increased. After high doses of DALA, locomotor activity in the center and at the periphery of the box were decreased. Frequency of rearing was either not affected or decreased by DALA treatment. DALA injected in the SN resulted in a small increase in frequency of hole visits and did not affect rearing and locomotor activity. DALA injection in the HPC had no effect on investigatory and spontaneous motor behaviour. The results are discussed in terms of a modulatory role of endogenous enkephalin on mesolimbic dopamine neurons.
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  • 138
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    Keywords: 8-OH-DPAT ; Feeding ; Chewing ; Liquid diet ; Choice test ; Rat ; 5-HT1A receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There have been recent claims that the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) elicits chewing and eating of solid but not liquid foods. Therefore, the effects of 8-OH-DPAT and another 5-HT1A agonist gepirone on the consumption of a liquid chow diet, by free feeding male rats, were examined. Both drugs produced a dose-dependent increase in the consumption of liquid diet during a 2 h test. The doses of 8-OH-DPAT and gepirone which increased liquid diet intake in this study were in the same range as those which were found previously to increase food pellet consumption by free feeding rats. The effects of 8-OH-DPAT were also examined in a feeding choice test in which free feeding animals were allowed to choose between food pellets and a liquid chow diet. In this test, 8-OH-DPAT significantly increased total food intake (liquid plus pellet) but had no significant effect on the consumption of either liquid or pellet diets when analysed separately. Thus, there were large individual differences in diet choice after 8-OH-DPAT injection. However, rats did not consistently choose to eat food pellets rather than the liquid diet, as would be predicted if the drug elicited chewing rather than eating. These results provide strong evidence that 8-OH-DPAT elicits a behaviourally specific hyperphagia and not chewing or gnawing.
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  • 139
    ISSN: 1432-2072
    Keywords: Anxiety ; Depression ; Novelty-suppressed feeding ; Diazepam ; Adinazolam ; Desipramine ; Amitriptyline ; Ro15-1788 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have examined the anxiolytic activity of acute and chronic antidepressant treatment in an animal model of anxiety involving novelty-suppressed feeding. Rats were food deprived for 48 h, placed into a novel environment containing food, and the latency to begin eating was recorded. Chronic (21 days), but not acute injections of desipramine (DMI; 10 mg/kg) and amitriptyline (AMI; 10 mg/kg) significantly reduced the latency to begin eating compared to controls, but the percentage decrease was not as great as that seen with either acute or chronic treatment with diazepam (2 mg/kg) or adinazolam (20 mg/kg). A time course study indicated that at least 2 weeks of treatment was necessary to observe a significant anxiolytic effect of antidepressants. The anxiolytic effect of the antidepressants was specific to the novel environment, as 2 weeks of treatment with either diazepam or DMI did not influence the latency to begin eating in the home cage. Finally, a single dose of the central benzodiazepine receptor antagonist, Ro15-1788 (20 mg/kg), given 15 min prior to testing, did not block the anxiolytic effects of chronic DMI, while it completely eliminated the effect of chronic diazepam treatment. These data suggest that antidepressants acquire anxiolytic properties following chronic administration and that this effect appears to be independent of the benzodiazepine receptor system.
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  • 140
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    Psychopharmacology 95 (1988), S. 344-350 
    ISSN: 1432-2072
    Keywords: Anticholinergic drug effect ; Age drug sensitivity ; Environmental interaction ; Grooming ; Social investigation ; Social grooming ; Agonistic interactions ; Play fighting and immobility ; Reintroduction procedure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The modulation of spontaneous (social and individual) behaviour as a function of the age of the rat (1, 3, 6, 12, 18 and 24 months) and of scopolamine dose (0.1, 0.2, 0.3 and 0.5 mg/kg) was studied. Observations were conducted during the dark phase of the reverse light/dark schedule using a reintroduction procedure. Results showed a marked effect of scopolamine on most of the behavioural patterns considered. Environmental interaction was enhanced whilst agonistic and social active interactions (social grooming) and play fighting were reduced by the drug. A slight hyposensitivity in the youngest rats and a marked hyposensitivity to the drug in the oldest ones were observed. The relationship to biochemical data and human sensitivity on the one hand and to learning and memory tasks and cholinergic specificity on the other hand, are discussed.
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  • 141
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Cocaine ; Tolerance ; CNS stimulants ; Rat ; Amphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate cocaine, 10.0 mg/kg, using a two-lever operant procedure. Dose-effect data were determined for the substitution of cocaine, diethylpropion, methylphenidate, phenmetrazine, phentermine, and fenfluramine for the cocaine stimulus. All of these drugs, except fenfluramine, substituted fully for the cocaine stimulus. Subsequently, training was halted and cocaine, 20 mg/kg/8 h, was administered for 9 days, and dose-effect data were redetermined for all of these drugs on days 7–9 of chronic administration. Chronic administration of cocaine produced tolerance to the stimulus properties of cocaine, and cross-tolerance to the stimulus properties of methylphenidate, phenmetrazine, and phentermine, such that doses approximately two-fold higher than those used acutely were necessary to reproduce the original effect; the potency for the substitution of diethylpropion for the cocaine stimulus was decreased greater than four-fold; and fenfluramine still failed to substitute for the cocaine stimulus. These data suggest that 1) a common mechanism may mediate tolerance to the discriminative stimulus properties of cocaine, methylphenidate, phenmetrazine, and phentermine, and 2) tolerance in the drug discrimination procedure may have potential for establishing a comprehensive evaluation of dependence liability of CNS stimulants.
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  • 142
    ISSN: 1432-2072
    Keywords: Haloperidol ; Partial reinforcement ; Continuous reinforcement ; Extinction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of haloperidol 0.1 mg/kg on the partial reinforcement extinction effect (PREE) paradigm at one trial a day, were examined. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasirandom 50% schedule. All animals were then tested in extinction. Haloperidol 0.1 mg/kg was administered in a 2 × 2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction of partially reinforced as compared to continuously reinforced animals, was obtained in all four drug conditions. The administration of haloperidol in acquisition increased markedly resistance to extinction in CRF animals. The administration of the drug in extinction decreased resistance to extinction in both CRF and PRF animals. The results are explained in terms of two independent actions of haloperidol: the well-known effect of reduction in the effectiveness of reinforcement as well as enhancement of the effectiveness of nonreinforcement.
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  • 143
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    Psychopharmacology 95 (1988), S. 553-555 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Physostigmine ; M1 receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate 0.10 mg/kg SC physostigmine from saline in a two-lever food-reinforced task. There was generalization to the acetylcholine esterase inhibitor THA as well as to the muscarinic receptor agonists arecoline, oxotremorine and RS 86, but not to neostigmine or nicotine. The physostigmine cue was blocked by SC scopolamine hydrobromide and by ICV pirenzepine, but not by scopolamine methylbromide or by mecamylamine. These antagonism studies suggest that the discriminative cue elicited by physostigmine might be mainly mediated by central M1 receptors.
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  • 144
    ISSN: 1432-2072
    Keywords: 5-HT1A receptors ; 5-HT1B receptors ; 5-HT1C receptors ; RU24969 ; TFMPP ; Feeding ; 8-OH-DPAT ; Hypothalamus ; Paraventricular nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The 5-HT1B agonist RU24969 when given either systemically (1 mg/kg SC) or by infusion (0.5, 1.0, 2.0 μg) into the region of the paraventricular nucleus of the hypothalamus caused dose-dependent hypophagia in rats previously deprived of food for 18 h. Similar results were obtained at the above dosages of 1-[3-(trifluoromethyl) phenyl] piperazine (TFMPP), which acts on 5-HT1B and possibly also on 5-HT1C receptors. Neither drug significantly affected locomotion following central administration. Food intake was significantly decreased when the 5-HT1A agonist 8-OH-DPAT was given systemically (1 mg/kg SC) to rats previously deprived of food but was unaffected when 8-OH-DPAT (1 μg) was infused into the paraventricular nucleus of both food-deprived and free feeding rats. Therefore, hypophagia occurs when hypothalamic 5-HT1B (and possibly 5-HT1C) but not 5-HT1A receptors are activated.
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  • 145
    ISSN: 1432-2072
    Keywords: Amphetamine ; Striatum ; Stereotypy ; Microinjection ; Oral behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amphetamine and other psychostimulant drugs induce perseverative motor behavior in rodents, such as compulsive sniffing, licking and biting. Although it is known that this behavior, termed stereotypy, is a consequence of dopaminergic stimulation of the striatum, the precise localization of the site of activation is unclear. It is reported here that microinjection of amphetamine (20μg/0.5μl) into a circumscribed subregion of the striatum specifically produces intense oral stereotypy. It is proposed that this region, which corresponds to a small area within the ventrolateral striatum, contains motor circuitry critical to oral behavior, including feeding. The behavior elicited by amphetamine-induced stimulation of this area may represent a simple animal model in which to study certain orofacial dyskinesias.
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  • 146
    ISSN: 1432-2072
    Keywords: Butyrophenones ; Catalepsy ; Development ; Haloperidol ; Maturation ; Perphenazine ; Phenothiazines ; Ptosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Developing rats are far more sensitive than adults to the behavioral effects of haloperidol. The present results support the hypothesis that this change may reflect age-related changes in brain responses such as alterations in drug-receptor or drug-effector mechanisms. Dose-response studies of catalepsy and ptosis were conducted in male Sprague-Dawley rats aged 30, 56, or 100 days. Resulting dose-effect curves were approximately parallel and showed rightward shifts with highly significant progressive increases of ED50. Similar developmental decreases in drug sensitivity (3–6 ×) were found following systemic (PO or IP) administration of haloperidol or the phenothiazine neuroleptic perphenazine, which differ markedly in structure, potency, distribution, and metabolism. Age-related decreases in drug sensitivity (3–4 ×) were also found using intracerebroventricular (ICV) administration of both agents in an attempt to bypass potential “pharmacokinetic” influences. Since the age-dependent decrease in sensitivity to both neuroleptics was found during the rising phase of drug action (1st hour) and ranked: PO〉IP〉ICV, some change in absorption and distribution of both drugs may occur in addition to the apparently important maturational decrease in target-organ sensitivity indicated by the responses to direct ICV injection and by the similarity of results obtained with dissimilar agents.
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  • 147
    ISSN: 1432-2072
    Keywords: Benzodiazepine ; Diazepam ; Beta-carboline ; FG 7142 ; RO 15-1788 ; Schedule-induced polydipsia ; SIP ; Adjunctive behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although benzodiazepine agonists and inverse agonists have opposite effects on drinking elicited by water deprivation, there is much less information about the effects of these drugs on nonhomeostatic drinking. In this experiment the effects of diazepam (0.3–5.0 mg/kg), a benzodiazepine receptor agonist, and FG 7142 (1.0–9.0 mg/kg), an inverse agonist, were determined on drinking elicited by a FT-60 schedule of food delivery (SIP). Both diazepam and FG 7142 dose-dependently reduced SIP, measured as either licking or volume consumed. In addition, diazepam reduced panel pressing for food, decreased locomotor activity, and changed the time course of each behavior. In contrast, FG 7142 reduced schedule-induced drinking without significantly altering other behaviors. The antagonist RO 15-1788, when given in combination with these drugs, only partially restored the reductions in licking produced by diazepam, but was much more effective in reversing the effects of FG 7142 at doses of the antagonist that failed by themselves to affect responding. The opposite pattern of effects was seen on the volume of water consumed. These effects are discussed in terms of the behavioral and pharmacological specificity of these drugs.
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  • 148
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    Psychopharmacology 94 (1988), S. 115-118 
    ISSN: 1432-2072
    Keywords: Clozapine cue ; Drug discrimination ; Acetylcholine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate clozapine (CLZ; 5.76 mg/kg, IPt-30 min) in a two-lever operant task in which responding on the correct lever was reinforced with water under a fixed ratio 32 schedule. The ED50 of CLZ was 1.1 mg/kg. The CLZ cue was generalised to atropine (ED50=8.7 mg/kg), scopolamine (ED50=0.37 mg/kg) and fluperlapine (ED50=4.0 mg/kg), but not to non-cholinergic compounds, i.e. buspirone, diazepam, ketanserin, prazosin or SCH 23390. The peripherally-acting muscarinic antagonist methylscopolamine did not substitute for CLZ. Furthermore, the CLZ cue was marginally attenuated byd-amphetamine; a high dose of oxotremorine (1 mg/kg) appeared to block the CLZ cue (to 22%). However, this effect could not be evaluated statistically due to an insufficient number of animals responding. These results may indicate that the discriminative stimulus effects of CLZ primarily involve antagonism of central muscarinic acetylcholine receptors.
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  • 149
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    Psychopharmacology 94 (1988), S. 119-125 
    ISSN: 1432-2072
    Keywords: Place conditioning ; Cocaine ; Intraperitoneal and intravenous administration ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been shown that pretreatment with dopamine (DA) receptor blockers disrupts the effect of intravenously (IV) and intracerebrally (ICV), but not intraperitoneally (IP) administered cocaine on place preference conditioning (PPC). The present study was undertaken to further evaluate possible differences between IV and IP cocaine PPC. To this end, several factors which may differentially influence IV and IP cocaine PPC were examined. Firstly, dose-response effects were studied. Intravenous cocaine produced PPC within a narrow dose range (0.5–2.5 mg/kg). Animals receiving IV injections of 5 and 10 mg/kg cocaine experienced convulsions and did not show PPC. For IP cocaine a 10-fold increase in dose (10 mg/kg) and twice the number of training trials was required in order to obtain PPC equal in magnitude to that with IV cocaine (0.5 mg/kg; two trials). Cocaine PPC was retained at least 1 month. Following IV cocaine preference developed for the side associated with the drug regardless of whether the conditioning was to the least or most preferred side. After IP cocaine, preference developed for the drug side only when the drug was paired with the least preferred side. Rats trained with IV, but not IP, cocaine significantly preferred the drug familiar side to a novel compartment. Preference for the IV or IP cocaine side developed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation of the cocaine PPC. The results show PPC procedure to be a valid test for evaluating rewarding properties of IV cocaine. However, they fail to show rewarding effects of IP cocaine.
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  • 150
    ISSN: 1432-2072
    Keywords: Nicotine ; Ageing ; Body weight ; Water intake ; Locomotor activity ; Exploratory behavior ; Memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To assess the effects of long-term treatment with nicotine on several behavioral measures (locomotor activity, exploratory efficiency, habituation, short-term and long-term memory) of young (5 months) and old (22 months) rats in a hexagonal tunnel maze, nicotine was added to the drinking water (0, 20 or 50 mg/l) for up to 131 experimental days. With the exception of effects on exploratory efficiency, young and old rats did not differ in their response to the drug. Nicotine decreased body weight throughout the experiment. Nicotine treatment reduced water intake during the first 30 min of the daily 4.5 h access to drinking water. Nicotine increased locomotor activity throughout the experiment. When nicotine treatment was discontinued during a 7-day withdrawal period, locomotor activity immediately dropped to control values. Intertrial habituation was not affected by nicotine. Long-term nicotine treatment had an attenuating effect on exploratory efficiency in young rats; however, the drug did not influence performance in tasks measuring spatial memory. Finally, age increased weight, decreased locomotor activity and impaired exploratory efficiency and short-term memory. Age, however, did not affect the performance of the long-term memory task.
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  • 151
    ISSN: 1432-2072
    Keywords: μ, δ opioid receptors ; Inhibition of enkephalin catabolism ; Nucleus accumbens ; Nucleus caudatus ; Motor behavior ; Kelatorphan ; DAGO ; DTLET ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of selective agonists for δ opioid receptors: [D-Thr2, Leu5]-enkephalyl-Thr6 (DTLET) and μ receptors: [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAGO) and of (R)-3-(N-hydroxyl-carboxamido-2-benzylpropanoyl)-L-alanine (kelatorphan), a complete inhibitor of enkephalin degrading enzymes, on the motor activity of rats was examined after their local administration into the nucleus accumbens (NA) or nucleus caudatus (NC). In both structures DTLET dose dependently enhanced locomotor activity as measured in the open-field test. This strong effect was reversed by the selective δ antagonist: ICI 174,864. Contrastingly, DAGO induced hypoactivity followed by hyperactivity 150 min later. This biphasic effect was blocked by systemic injection of naloxone, but not by ICI 174,864. The physiological relevance of these effects was ascertained by the naloxone-reversible stimulatory responses induced by kelatorphan, supporting a role for endogenous enkephalins in the control of behavior through δ receptor stimulation.
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  • 152
    ISSN: 1432-2072
    Keywords: Alcohol drinking ; Brain amines ; Neonatal ; Open field ; Porsolt's swim test ; Propranolol ; Rat ; Sleep ; Spontaneous alternation ; Startle reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examined the effects of early postnatal treatment with a beta-adrenoceptor antagonist propranolol (5 mg/kg IP daily) on concomitant and subsequent behavior and central aminergic transmission in rats. During propranolol exposure from the 7th to the 20th postnatal days sleep-wake recordings, carried out with the static charge sensitive bed (SCSB) method, showed a decrease in the percentage of active sleep and an increase in waking. When the animals were 1–3 months of age, the open field behavior was changed, immobility time in the Porsolt's swim test was lengthened, and voluntary alcohol consumption was increased in the propranolol-treated rats. Neither motor reactivity to auditory stimuli nor spontaneous alternation behavior was affected. At the age of 4 months concentrations of brain amines and their metabolites were measured from several brain regions. In the propranolol-treated rats the noradrenaline levels were increased in the limbic forebrain and cerebellum. The results suggest that in rats the exposure to propranolol during the rapid growth period of cerebral catecholamine systems, and the concomitant alterations in sleep are related to later changes in behavior and to increased noradrenaline content in the limbic forebrain and cerebellum.
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  • 153
    ISSN: 1432-2072
    Keywords: Rat ; Dopamine receptors ; PHNO ; SKF 38393 ; Feeding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of selective D-2 and D-1 dopamine (DA) receptor agonists on food consumption were investigated in free-feeding rats. A selective D-2 receptor agonist, (+)-4-propyl-9-hydroxynaphthoxazine (PHNO), increased the consumption of standard food pellets in the dose range of 7.5–120 μg/kg, while SKF 38393 (5.0 mg/kg), a selective D-1 receptor agonist, decreased food pellet intake. The increase in food pellet intake produced by PHNO was blocked by haloperidol (an antagonist relatively selective for the D-2 receptor at the dose used, 0.05 mg/kg) and SCH 23390 (20 μg/kg, a D-1 receptor selective antagonist). Increasing “arousal” by disturbance associated with repeated food weighting also increased food pellet consumption, but did not diminish PHNO-elecited feeding. However, the same range of doses of PHNO (7.5–120 μg/kg) which increased food pellet intake decreased consumption of a liquid diet, and had no overall effect on a highly palatable liquid diet. The increase in consumption of solid food induced by PHNO appears to be secondary to enhancement of chewing behaviors. In contrast, the decrease in food intake induced by SKF 39393 may be due to a direct action of the drug on neural feeding mechanisms.
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  • 154
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    Psychopharmacology 94 (1988), S. 227-231 
    ISSN: 1432-2072
    Keywords: Adrenaline ; Naloxone ; Passive ; Avoidance ; Retention ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible involvement of endogenous opioid peptides in the development of the facilitatory effect of adrenaline on memory has been investigated. For this purpose post-training administration of adrenaline and/or naloxone was carried out in rats tested in an inhibitory avoidance paradigm and subjected or not to pre-training (extensive familiarization with the training situation prior to the acquisition trial). Adrenaline injected subcutaneously in a dose of 500 μg/kg facilitated retention performance in rats both subjected or not to pre-training. Naloxone administered SC (400 μg/rat) did not influence retention behaviour in rats subjected or not to pre-training, nor did ICV (0.80 ng/rat) administration. Interestingly, the opiate antagonist when injected SC (400 μg/rat) prevented the facilitatory effect exerted by adrenaline in pretrained as well as in not pre-trained rats. However, ICV administration of naloxone (0.80 μg/rat) dit not influence the behavioral effects exerted by the bioamine. These data suggested a role of endogenous opioid peptides on the facilitatory effect of adrenaline on memory, possibly independent of novelty factors and thus of the brain β-endorphin system. In addition, our results point to the periphery as the most likely site for such interaction.
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  • 155
    ISSN: 1432-2072
    Keywords: Dopamine ; Self-administration ; (+) Amphetamine ; Amygdala ; Nucleus accumbens ; 6-OHDA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of 6-OHDA lesions of dopamine terminals within the amygdala were investigated on i) (+) amphetamine-induced locomotor hyperactivity and ii) the acquisition of intravenous self-administration of (+) amphetamine. The lesioned rats exhibited increased locomotor activity in response to (+) amphetamine (0.75 and 1.5 mg/kg), but not at the higher dose (3 mg/kg). Self-administration of (+) amphetamine was also significantly greater than in controls. Biochemical analysis of the 6-OHDA-induced lesions of the amygdala indicated increased turnover of dopamine (DOPAC/DA) in the nucleus accumbens. We hypothesize that the behavioural effects were mediated by amygdala-accumbens interactions.
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  • 156
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    Psychopharmacology 94 (1988), S. 248-253 
    ISSN: 1432-2072
    Keywords: Bremazocine ; EKC ; Forward locomotion ; Grooming ; Open field ; Rat ; Rearing ; Tifluadom ; U-50,488H
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An observational analysis of the effects of four kappa-opioid agonists on forward locomotion, rearing and grooming displayed by rats in a novel open field was undertaken. The doses of agonists used corresponded to those previously found to produce changes in food consumption. Ethylketocyclazocine (0.1 and 1 mg/kg), bremazocine (0.01 and 0.1 mg/kg) and tifluadom (0.3 and 3 mg/kg) exerted suppressant effects on all the activities monitored. Grooming behaviour appeared to be particularly sensitive to this action, being virtually abolished by the larger doses of these compounds. In contrast, the selective kappa agonist U-50,488H (0.1–3 mg/kg) only attenuated grooming at the two highest doses tested (1 and 3 mg/kg). None of the agonists tested produced stimulation of open field activity during the 1-h study. Reductions in activity occurred at doses previously found to increase and decrease food intake. It was therefore concluded that the hyperphagia induced by kappa agonists was not part of a more general behavioural activation, whilst reductions in food consumption probably result from a non-specific behavioural depression.
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  • 157
    ISSN: 1432-2072
    Keywords: Physostigmine ; Rat ; Tolerance ; Fixed ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of environmental variables on the development of tolerance to physostigmine's effects in rats was examined using multiple fixed-ratio, extinction schedules of food presentation. Initial administration of physostigmine (0.4 mg/kg) produced nearly maximal decreases in the number of food pellets delivered, running response rate, and overall response rate, under multiple FR 10, EXT and multiple FR 50, EXT schedules. With repeated administration, tolerance to physostigmine's effects was observed when 10 responses were required to produce reinforcement but was not observed when 50 responses were required to produce reinforcement. Tolerance under the multiple FR 10, EXT schedule of reinforcement was also observed when physostigmine was administered post-session. When tolerance was acquired, it was retained for up to 25 drug-free days. These results suggest that tolerance to physostigmine's effects on schedule-controlled behavior is strongly influenced by response requirement, independent of physostigmine-induced reinforcement loss. Additionally, tolerance is not dependent on experience with the schedule while under the effects of physostigmine, and is retained for a substantial period of time in the absence of continued physostigmine administration.
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  • 158
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    Psychopharmacology 94 (1988), S. 359-364 
    ISSN: 1432-2072
    Keywords: Serotonin synthesis ; Dopamine synthesis ; RU-24969 ; Anxiety ; Antidepressant activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The regional brain synthesis of serotonin (5-HT) and dopamine (DA) was studied in rats after various doses of 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU-24969), a 5-HT1 receptor agonist. The potential anxiolytic and antidepressant properties of the compound were examined as well. RU-24969 0.62 mg/kg significantly reduced 5-HT synthesis in the nucleus accumbens and hypothalamus, while with 1.25 and 2.5 mg/kg the effect was also seen in striatum, hippocampus, brainstem and cortex. RU-24969 2.5 and 5 mg/kg had no effect on DA synthesis in the striatum, while 5.0 mg/kg significantly increased it in the nucleus accumbens. At doses of 2.5 and 5.0 mg/kg the drug increased the motor activity of rats measured during 1 h in activity cages while 0.625 and 1.25 mg/kg had no effect. Doses ranging from 0.62 to 2.5 mg/kg RU-24969 significantly reduced unpunished responding in a test of conditioned suppression of drinking. Doses of 1.25 and 2.5 mg/kg also reduced punished responding. Finally, of various doses only 2.5 mg/kg RU-24969 significantly reduced the duration of immobility of rats in the forced swimming test but the effects were due to running around the cylinder rather than to escape attempts. In conclusion, RU-24969 reduced 5-HT synthesis in all brain areas examined, with a preferential effect for the nucleus accumbens and the hypothalamus. At higher doses, there was also a specific increase in DA synthesis in the nucleus accumbens. The compound raised the level of activity of rats but no clear evidence of any potential anxiolytic or antidepressant properties has been obtained.
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  • 159
    ISSN: 1432-2072
    Keywords: Diazepam ; Memory ; Anterograde amnesia ; Retroactive interference ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were submitted to a training and a test session of shuttle avoidance. Exposure to a session of extinction of this task either 2 or 24 h after training interfered with retention test performance. Exposure to an open field 2, but not 24 h after the avoidance training also interfered with retention. Diazepam blocked the deleterious effect of extinction and of the open field on retention of the avoidance task. Diazepam alone had no effect when given after avoidance training; it did, however, also interfere with retention when given prior to training. It is likely, therefore, that diazepam cancelled the effect of the extinction or of the open field on avoidance retention because of anterograde amnesia (i.e., it prevented the recording of these tasks). The deleterious effect of the open field on retention of shuttle avoidance can be explained by retroactive interference caused by the addition of information. It is not due to a direct influence on retrieval, it is not due to extinction, and it had to be recorded 2 h after training in order to the effective.
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  • 160
    ISSN: 1432-2072
    Keywords: R(−)-2,5-Dimethoxy-4-77Br-amphetamine ; Rat ; 5-Hydroxytryptamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract R(−)-2,5-Dimethoxy-4-77Br-amphetamine [77Br-R(−)DOB], a radioligand of high specific activity (1500±200 Ci/mmol), was used to label membrane-associated recognition sites in rat brain. 77Br-R(−)DOB sites were of high affinity (K D=0.19 nM) but low density (B max=0.32 pmol/g tissue) in rat brain preparations. Competition experiments show that both 5-hydroxytryptamine (5-HT) and 5-HT2 antagonists display nanomolar potency for these sites. We conclude that 77Br-R(−)DOB labels 5-HT recognition sites in rat brain which do not fit into current classifications of 5-HT binding subtypes. This finding may be of aid in deciphering the mechanism of action of hallucinogens in man.
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  • 161
    ISSN: 1432-2072
    Keywords: Bromocriptine ; Apomorphine ; Reserpine ; α-Methyl-p-tyrosine ; SK&F38393 ; SCH23390 ; Yawning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ability of bromocriptine (BRC), a selective dopamine D-2 receptor agonist, to induce yawning responses was studied in rats pretreated with reserpine and α-methyl-p-tyrosine (α-MPT). BRC (1–20 mg/kg IP) evoked yawning responses, which were pronounced at 2.5 mg/kg and characterized by the head moving downward. Higher doses of BRC (5–20 mg/kg) dose-dependently delayed the onset and peak time of yawning. A low dose of the selective D-1 dopamine receptor agonist SK&F38393 did not induce yawning but enhanced the BRC-induced response. Pretreatment with reserpine (1 and 5 mg/kg SC), α-MPT (100 and 300 mg/kg IP) and reserpine (1 mg/kg) plus α-MPT (100 mg/kg) was able to significantly reduce BRC-induced yawning. The inhibitory effects were prevented by a low dose of SK&F38393 (0.5 mg/kg IP). In particular, combined treatment with reserpine (5 mg/kg) and BRC (10 and 20 mg/kg) elicited upright fighting and jumping behaviors which were inhibited by haloperidol (1 mg/kg IP), a non-selective D-1 and D-2 receptor antagonist, SCH23390 (0.05 mg/kg SC), a selective D-1 receptor antagonist, or sulpiride (20 mg/kg IP), a potent D-2 receptor antagonist, and were potentiated by SK&F38393 (0.5 mg/kg). SCH23390 (0.05 mg/kg) decreased BRC-induced yawning and the apomorphine (low doses)-induced potentiation of BRC yawning, and prevented the apomorphine (high doses)-induced reduction of BRC yawning. SCH23390 also inhibited apomorphine-induced stereotypy and BRC-induced potentiation of apomorphine stereotypy. Furthermore, haloperidol (0.02 and 1.0 mg/kg IP), sulpiride (20 mg/kg IP) or scopolamine (0.5 mg/kg IP) inhibited BRC-induced yawning, but prazosin (1.0 and 3.0 mg/kg IP), an α-1 receptor antagonist, did not affect this behavior. These results suggest that BRC-induced yawning may be mediated via presynaptic dopaminergic neuron activity and that BRC, in addition to the stimulation of dopamine D-2 receptors, appears to require endogenous dopamine or receptor activation by another dopamine agonist (D-1 agonist) for the induction of yawning, stereotypy and upright fighting responses. The ability of dopamine agonists to induce these behaviors seems to depend apon the potency and ratio of D-2 versus D-1 receptor activity.
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  • 162
    ISSN: 1432-2072
    Keywords: Bromocriptine ; Apomorphine ; Physostigmine ; Pilocarpine ; Yawning ; Stereotypy ; Dopaminergic-cholinergic interaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bromocriptine (BRC), a dopamine D-2 receptor agonist, physostigmine, an anticholinesterase agent and pilocarpine, a muscarinic cholinergic receptor agonist, produced yawning in rats, with the most effective doses being 2.5 mg/kg, 0.2 mg/kg and 4 mg/kg, respectively. BRC-induced yawning was inhibited by high doses of SK&F38393 (5 and 10 mg/kg), a selective D-1 receptor agonist. BRC or SK&F38393 alone did not induced stereotyped behaviors. However, when BRC was administered after SK&F38393 (5.0 and 10 mg/kg), stereotyped behaviors occurred; i.e., mainly sniffing at 2.5 and 5.0 mg/kg BRC, and mainly licking and biting 10 and 20 mg/kg BRC. A high dose of apomorphine (4 mg/kg IP) completely inhibited physostigmine-induced yawning (physostigmine yawning) but did not affect pilocarpine-induced yawning (pilocarpine yawning). BRC (2.5–20 mg/kg) increased physostigmine yawning in an additive fashion. Pilocarpine yawning was completely blocked by either low or high doses of BRC. The inhibitory effect of BRC on pilocarpine yawning was reversed by sulpiride (20 mg/kg). α-Methyl-p-tyrosine (α-MPT; 100 and 200 mg/kg) did not affect physostigmine yawning but diminished pilocarpine yawning. Furthermore, physostigmine (0.2 mg/kg) inhibited apomorphine (4.0 mg/kg)-induced hyperlocomotion and sniffing but not licking and biting, whereas pilocarpine (4.0 mg/kg) had the opposite effect. These results suggest that activation of postsynaptic dopamine receptors (primarily D-1 receptors) may inhibit cholinergic neurons activated by cholinesterase inhibition, i.e., endogenous acetylcholine, and that the postsynaptic sensitivity of cholinergic neurons to a direct acetylcholine agonist (muscarinic M-1 receptor agonist) may be reduced by stimulation of presynaptic dopamine receptors (D-2 receptor) and/or inhibition of dopamine synthesis.
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  • 163
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    Pflügers Archiv 413 (1988), S. 62-66 
    ISSN: 1432-2013
    Keywords: Erythropoiesis ; Erythropoietin ; Renal artery constriction ; Hypoxia ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is generally assumed that the O2 supply to the kidneys is the major determinant of the synthesis of erythropoietin (Ep). In the present study, the O2 supply of the kidneys of rats was lowered by the reduction of renal blood flow (rbf). Plasma Ep was determined after about 18 h of bilateral application of Goldblatt clips with graded inner diameters. The results were compared to findings in anemic rats, in which the systemic O2 supply was lowered by exchange transfusion of blood with plasma. We found a linear correlation between Ep levels in plasma and the degree of reduction of rbf. However, there was an exponential relationship between Ep levels and the concentration of hemoglobin in blood. In addition, the elevation of plasma Ep was only moderate, when rbf was reduced (maximum 0.07 IU Ep/ml plasma). The increase in Ep concentration was much more pronounced in anemia (up to about 7 IU Ep/ml plasma). From these results it may be concluded that decreasing oxygen supply to the kidney through reduction in renal blood flow (ischemic hypoxia) is less effective in increasing erythropoictin production than reducing the hemoglobin concentration (anemic hypoxia). The possibility must be considered that the increase in renal production of erythropoietin due to anemic hypoxia is triggered by one or more extrarenal signals.
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  • 164
    ISSN: 1432-2013
    Keywords: Chloride channel ; Rat ; Skeletal muscle ; Stereoisomers ; 2-(p-chloro-phenoxy) isobutyric acid ; Clofibric acid ; Myotonia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The S-(−) isomers of a series of clofibric acid analogs produced only a block of chloride conductance of rat skeletal muscle fibers with increasing concentrations until block was nearly complete. The R-(+) isomers, on the other hand, at low concentrations increased chloride conductance by as much as 9% to 39% and at higher concentrations decreased chloride conductance, but never by more than 27% of the control value. The actions of the enantiomeric pairs to either produce or inhibit myotonic excitability paralleled their ability to block or increase chloride conductance, respectively.
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  • 165
    ISSN: 1432-2307
    Keywords: Mammary neoplasms ; DMBA ; Rat ; Carcinoma ; Sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mammary tumours were induced by the direct dusting of 1 mg, 7,12-dimethylbenz(a)anthracene (DMBA) powder onto the mammary gland of both 30-day-old female and male Sprague-Dawley rats, and the tumours were examined histologically. Mammary tumours developed in 43/43 (100%) of the females 11 to 20 weeks after DMBA dusting and 16/23 (70%) of the males 18 to 28 weeks after dusting, while non-mammary spindle cell sarcomas occurred in 5/23 (22%) of the males 15 to 24 weeks after dusting. A variety of benign and malignant mammary tumours of epithelial and/or mesenchymal origin were induced, which are comparable to human mammary tumours. Different histological patterns were observed in different areas of the same tumours. Ovariectomy revealed hormone (ovary)-dependency in 10/17 (59%) of the tumours, revealing regressing epithelial and proliferating mesenchymal tumour elements on histological examination.
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  • 166
    ISSN: 1432-1912
    Keywords: Calcitonin gene-related peptides ; Tachykinins ; Capsaicin ; Cardiac sensory nerves ; Rat ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effects of calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide K (NPK) and substance P (SP) on contractility of the guinea-pig and rat heart were studied in vitro in relation to the response to capsaicin. 2. Human (h) CGRP alpha (a) and beta (β) were equipotent in stimulating the contractile force and rate of the spontaneously beating guinea-pig right atrium. 3. Both NKA and NPK inhibited contractile force and rate in the guinea-pig atrium whilst a mainly negative chronotropic effect was observed in the whole heart. SP did not influence cardiac contractility. 4. Human CGRP α and β mimicked the contractile effects of capsaicin in the guinea-pig atrium. In the whole heart preparation, hCGRP α and capsaicin increased heart rate whereas capsaicin also evoked an atropine-resistant inhibition of contractile force. The stimulatory effect of capsaicin on heart rate was absent after systemic capsaicin pretreatment, while the inhibition of ventricular contractile tension remained unchanged. 5. Extended incubation with hCGRP α or β was associated with development of cross-tachyphylaxis between these two agents in the guinea-pig atrium. However, CGRP tachyphylaxis did not change the atrial response to noradrenaline, forskolin or NKA. The stimulatory effects of capsaicin on atrial contractility were absent after tachyphylaxis to hCGRP α or β. 6. There was no detectable supersensitivity to the stimulatory effects of rat (r) CGRP α on the spontaneously beating atrium after capsaicin pretreatment of adult or neonatal rats. In conclusion the present data provide further evidence that the capsaicin-induced stimulation of atrial contractility is due to local release of CGRP. CGRP tachyphylaxis seems to be a specific, receptor-mediated event and is not related to down-regulation of the adenylate cyclase system. The inhibition of the contractile force in whole heart preparations by capsaicin is most likely due to a non-cholinergic effect independent of tachykinin release.
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  • 167
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 463-471 
    ISSN: 1432-1912
    Keywords: 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] ; 5-HT1A receptors ; CNS ; 5-HT synthesis and release ; Hemitransection ; Dorsal raphé application ; Regulation of 5-HT activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was undertaken in an attempt to assess whether the effects of the potent and selective 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, on cerebral 5-hydroxytryptamine (5-HT) neurochemistry in vivo are mediated via 5-HT autoreceptors on the cell bodies or on the terminals, and/or via postsynaptic 5-HT receptors. To this end we determined in vivo indices of 5-HT synthesis and release/turnover rates in a number of prominent 5-HT neuronal projection areas in the CNS i) after systemic administration of 8-OH-DPAT to rats with an acute unilateral axotomy of the ascending mesencephalic monoamine neurones, or ii) after local infusion of the compound into the dorsal raphé (DRN) 5-HT cell body region of intact rats. Transection did not alter 5-HT synthesis per se, but prevented the synthesis-inhibitory effect of 8-OH-DPAT. Thus, the 5-HT synthesis-inhibiting action of 8-OH-DPAT is highly dependent upon intact impulse flow in the central 5-HT neurones. On the other hand, local DRN application of the compound (1 μg) resulted in a clearcut reduction of the 5-HT synthesis and release indices measured in 5-HT terminals in, e. g., the striatum. These findings provide direct neurochemical evidence that by preferentially stimulating somatodendritic 5-HT1A receptors, 8-OH-DPAT inhibits the 5-HT neuronal impulse flow, thereby effectuating decreased terminal 5-HT synthesis and release. Taken together, the data are consistent with the suggestion that 8-OH-DPAT acts as an agonist preferentially at cell body vs. terminal 5-HT autoreceptors, therefore also emphasizing the distinction between terminal and cell body 5-HT autoreceptors. The results obtained may have important implications for the understanding of mechanisms involved in regulating the activity of central serotoninergic neurones.
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  • 168
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 96-98 
    ISSN: 1432-1912
    Keywords: Histamine ; Gastric acid secretion ; Central nervous system ; Vagus nerve ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Administration of 10–100 μg of histamine into the lateral cerebral ventricle of anaesthetized rats stimulated gastric acid secretion in a dose-dependent manner, while subcutaneous (s. c.) injections of the same doses produced clearly less pronounced increases in the acid output. In vagotomized rats only a marginal response to histamine given into the lateral ventricle was observed. When injected into the third cerebral ventricle the doses of histamine needed for the stimulation of gastric acid secretion were 1–10 μg, the effect being totally abolished by vagotomy. The results indicate that histamine is capable of stimulating gastric acid secretion by a central, vagal-dependent mechanism.
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  • 169
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 345-349 
    ISSN: 1432-1912
    Keywords: 5-HT ; Tryptophan hydroxylase ; Sex difference ; Brain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have revealed that brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) are moderately higher in female than in male rats. Since tryptophan hydroxylase is only about half saturated with substrate, the greater availability of precursor in female rats might contribute to their higher 5-hydroxyindole levels. The present investigation was aimed at clarifying whether there is a sex difference in central tryptophan hydroxylase capacity. Hence, both sexes received a high dose of l-tryptophan (400 mg/kg), which resulted in a tenfold increase in brain tryptophan concentrations and presumably a virtual saturation of tryptophan hydroxylase. Following such treatment, 5-hydroxytryptophan (5-HTP) levels, measured after l-amino acid decarboxylase inhibition, were compared in males and females. Both in saline-and l-tryptophan-treated rats, 5-HTP levels were generally higher in females. In another group of animals, receiving 400 mg/kg of l-tryptophan as sole treatment, 5-HT and 5-HIAA concentrations were measured. As in the case of 5-HTP, the higher 5-HT and 5-HIAA levels observed in females persisted after l-tryptophan treatment. The present data suggest that brain tryptophan hydroxylase activity is greater in females; this sex difference probably contributes to the higher 5-HT and 5-HIAA levels in females.
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  • 170
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    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 1-8 
    ISSN: 1432-1912
    Keywords: 5-Hydroxytryptamine ; 5-HT receptors ; 5-Carboxamidotryptamine ; Rat ; Cardiovascular
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Peripheral 5-HT receptor-mediated responses were examined in pithed spontaneously hypertensive rats and normotensive wistar rats. Responses examined were: Pressor and depressor responses, tachycardia and inhibition of stimulation-evoked tachycardia. In pithed spontaneously hypertensive rats, 5-HT, but not the 5-HT1-selective agonist 5-carboxamidotryptamine, produced pressor responses, and these were potently antagonised by the 5-HT2-selective antagonists ketanserin and LY 53857. In pithed spontaneously hypertensive rats, the tachycardia to 5-HT was abolished by a combination of the 5-HT2 receptor antagonist LY 53857 and propranolol, suggesting that the tachycardia is mediated by 5-HT2 receptors and by release of noradrenaline. In pithed spontaneously hypertensive rats, 5-carboxamidotryptamine, 5-HT, and to a lesser extent the 5-HT1 receptor agonist RU 24969, but not the 5-HT1A receptor agonist 8-OH-DPAT, produced depressor responses which were antagonised by methysergide and metitepin, but which do not clearly fit with any of the 5-HT, ligand binding sites. In pithed normotensive wistar rat, 5-carboxamidotryptamine was approximately 100 times more potent than 5-HT and 8-OH-DPAT at inhibiting the cardio-acceleration produced by single pulse electrical stimulation and this inhibition was antagonised by metitepin, so that the response is mediated by 5-HT1 receptors.
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  • 171
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    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 164-168 
    ISSN: 1432-1912
    Keywords: Central nervous system ; Alpha-2 adrenoceptors ; Oxymetazoline ; Vagus nerve ; Pituitary gland ; Vasopressin ; Gastric secretion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The mechanism of the gastric antisecretory action of the stimulation of central alpha-2 adrenoceptors were studied in conscious, pylorus-ligated rats using intracerebroventricularly (i.c.v.) administered oxymetazoline as the model substance. I.c.v. administration of 10 μg of oxymetazoline strongly inhibited the secretion of acid, pepsin and fluid, whereas upon s.c. injection this dose was without any effect. Pretreatment with idazoxan abolished the antisecretory effect of i.c.v. administered oxymetazoline. I.c.v. injected oxymetazoline inhibited gastric secretion induced by carbachol in vagotomized rats, but the inhibitory effect was less pronounced than on the spontaneous secretion in rats with intact vagi. Hypophysectomy abolished the antisecretory effect of i.c.v. oxymetazoline, and pretreatment with the vasopressin antagonist, d(CH2)5Tyr(Me)AVP, significantly attenuated it. The results suggest that the inhibition of gastric secretion by the stimulation of central alpha-2 adrenoceptors in rats is mediated in part by vasopressin released from the pituitary gland.
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  • 172
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 287-292 
    ISSN: 1432-1912
    Keywords: PYY ; Rat ; Non-adrenergic ; Non-cholinergic ; In vitro ; Small intestine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of peptide YY (PYY) on motor activity of the rat small intestine, were studied using isolated organ bath preparations arranged for recording muscle activity in the longitudinal axis. PYY induced TTX sensitive concentration-dependent contractions and/or relaxations of the longitudinal muscle in different regions of the small intestine. In the duodenum PYY evoked only “cholinergic” contractions (3 × 10−8−3 × 10−7 M). In the jejunum, PYY-evoked concentrations were non-cholinergic, and contractions were never seen in the ileum. In the jejunum and ileum, PYY-evoked relaxations (3 × 10−3 × 10−7 M) were unaffected by adrenoceptor or cholinergic receptor blockade, thus indicating that these relaxations were mediated by non-adrenergic, non-cholinergic (NANC) inhibitory nerves. Another action of PYY was to cause inhibition of field stimulation-evoked cholinergic concentrations. This inhibitory action was primarily due to antagonism of post-junctional, cholinergic receptor mediated events. In addition, PYY inhibited histamine evoked contractions of the longitudinal muscle. All regions of the small intestine could be desensitized to PYY. Such PYY-densensitization did not affect the ability of the longitudinal muscle to relax in response to applied ATP or papaverine. These results suggest PYY has potent concentration-dependent stimulatory actions at intrinsic inhibitory and excitatory motor nerves. In addition, PYY interferes with contractions but not relaxations of the longitudinal muscle.
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  • 173
    ISSN: 1432-0738
    Keywords: (14C)-2-ethylhexyl acrylate ; Rat ; Distribution ; Elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The fate of (14C)-2-ethylhexyl acrylate was studied in adult male Wistar rats given an intravenous (i.v.) or intraperitoneal (i.p.) injection of 10 mg/kg (0.054 mmol/kg). The elimination of radioactivity from blood was bi-exponential, irrespective of the route of (14C)-2-EHA administration or the age (weight) of the rats. The first phase half-lives after i.v. and i.p. administration in 4-month-old rats were 30 and 60 min, in 7-month-old rats 115 and 130 min, respectively. The corresponding values for the slow-phase were 5 and 6 h, and 14 and 14h. Elimination of the radioactivity from tissues followed a pattern similar to that seen for blood. More than half of the administered radioactivity was exhaled as carbon dioxide. Exhalation of unchanged (14C)-2-EHA accounted for only 0.05% (i.v.) or 0.3% (i.p.) of the initial dose of radioactivity. The radioactivity excreted in the urine within the first 24 h posttreatment accounted for 7% (i.p.) or 14% (i.v.) of the initial dose, and only 2% was excreted as thioethers.
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  • 174
    ISSN: 1432-0738
    Keywords: Gentamicin ; Pregnancy ; Rat ; Fetus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract As part of our studies on the prenatal induction of renal dysfunctions in rats by gentamicin we measured maternal plasma levels of the drug. Additionally, the gentamicin concentrations in the plasma of rat fetuses after single s.c. injections of gentamicin were measured. The following results were obtained: 1) Non-pregnant rats excrete the drug faster than pregnant rats; 2) after a single s.c. injection of 110 mg gentamicin/kg body wt to six pregnant rats on day 21 of gestation the following pharmacokinetic variables were calculated: t1/2(inv): 27.0±6.1 min, t1/2(elim): 54.7±3.8 min, Cmax: 166.2±22.7 mg/l, tmax: 53±6.7 min, AUC: 431.7±53.4 mg/l×h; 3) plasma concentrations increase with the duration of pregnancy; 4) fetal plasma concentrations were determined between 45 and 660 min after single injections of 150 mg/kg to the dams. The concentrations showed minimum variation over this time period. Thus, the ratio of maternal to fetal plasma levels decreases drastically during this period; 5) 8 h after s.c. injection of 110 mg/kg to six dams (day 21 of gestation) individual plasma concentrations in the plasma of mother animals and in the plasma of 65 fetuses were determined. All fetal plasma samples showed higher concentrations than the corresponding maternal ones; 6) after multiple injections a significant increase in plasma concentrations can be seen. A considerable individual variance is obvious at all times and with both doses investigated; 7) since maternal plasma concentrations vary considerably in individual animals, especially after multiple injections, fetal exposure must also be variable in different litters. This would also affect the extent of postnatal dysfunction in various litters.
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  • 175
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    Archives of toxicology 61 (1988), S. 373-377 
    ISSN: 1432-0738
    Keywords: Dibutyltin dilaurate ; Neurotransmitters ; Brainareas ; Behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exposure to DBTL (20, 40 or 80 mg/kg body weight) caused a decrease in levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) at all treatment levels. Hypothalamus and frontal cortex appeared to be most affected, since levels of all the three amines examined showed changes in these areas. Maximum decrease of DA was found in corpus striatum, NA in pons medulla and of 5-HT in frontal cortex. These animals also showed a decrease in spontaneous locomotor activity and learning at all the doses. The data indicates involvement of hypothalamus and frontal cortical regions of the brain in the neurotoxicity of DBTL.
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  • 176
    ISSN: 1432-0738
    Keywords: Acyclovir ; Prenatal toxicity ; Rat ; Viru-statics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pregnant rats were treated during organogenesis with s.c. injections of acyclovir and the embryos were evaluated on day 11.5 of gestation (crown-rump length, somites, protein content, score, abnormalities, histological examination). After eight injections of 50 mg/kg body wt on days 9, 10, and 11 of pregnancy a reduction of the crownrump length was noticed. After 100 mg/kg this effect was more pronounced. With two or three applications of this dose on day 10 specific embryonic abnormalities were visible: the shape of the head was abnormal, the width of the skull had decreased resembling a beak-like visceral cranium. With a single administration of 200 mg/kg on day 10 we found a similar but slightly more pronounced outcome. A drastic change of all variables was obtained after eight injections of 100 mg/kg on days 9, 10, and 11. Comparatively we measured maternal plasma concentrations of acyclovir 1 h after the administration of 50, 100 or 200 mg/kg body wt. After an injection of 50 mg/kg on days 9, 10, and 11 of gestation (three injections/day) the plasma levels ranged from 19.1 to 40.0 mg/l (1 mg/l = 4.44 μM). No cumulation was observed. In contrast, a cumulative effect was detected following a dose of 100 mg/kg. After the first injection of this dose a mean value (± SD) of 60.3±14.7 mg/l (n = 16) was obtained. In this case a third injection increased the mean plasma level to 124.6±16.6 mg/l (n = 5). Further injections, however, led to decreasing levels. One hour after administration of 200 mg/kg body wt acyclovir levels ranged from 120.0 to 163.9 mg/l. We conclude that acyclovir, at doses leading to plasma concentrations well above the therapeutic level in the dam, interferes with the embryonic development in the rat. Acyclovir induces typical gross structural abnormalities which have been first observed using a whole embryo culture system.
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  • 177
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    Archives of toxicology 61 (1988), S. 489-495 
    ISSN: 1432-0738
    Keywords: Fusarenon-X ; T-2 Toxin ; Jejunal absorption ; Monosaccharide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to delineate the effects of Fusarenon-X (FX) and T-2 toxin (T-2) on intestinal absorption of monosaccharide, jejunal absorption in vivo and uptake in vitro of 3-0-methyl glucose (m-glucose) and l-glucose were studied in rats. Jejunal absorption in vivo was assessed by determining the rate of appearance of the sugars in plasma of the mesenteric vein draining the jejunal segment, which was perfused with the medium containing radiolabelled m-glucose or l-glucose. Jejunal uptake in vitro was assessed by determining the m-glucose or l-glucose uptake by the everted jejunum taken from toxin-treated rats, m-Glucose absorption was reduced 1 or 3 h after either toxin was injected into the jejunal lumen. A reduction of m-glucose absorption was also noted after intravenous injection of the toxins, although the timing and magnitude of the reduction were slightly different from those seen after the luminal injection. These results suggest that both toxins impair the jejunal function relating to monosaccharide absorption in the early stages of intoxication. The reduction in m-glucose absorption was associated with a reduction in l-glucose absorption and unchanged or increased uptake of l-glucose. The active transport component, which was indicated by the difference between absorption or uptake of the two sugars, was also reduced in association with the reduction of m-glucose absorption. These results suggest that the toxins cause specific damage in the active transport system for monosaccharides on the one hand, and impairment of their diffusional movement from the epithelial layer to the mesenteric vein on the other.
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  • 178
    ISSN: 1432-0738
    Keywords: Lysozyme ; Renal damage ; Urinalysis ; Radioimmunoassay ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The radioimmunoassay (RIA) as a high sensitive detection method for rat lysozyme (LZM) was established and applied to determine LZM excretion in urine from rats treated with tubulotoxic chemicals in order to establish a sensitive method of detecting minor renal damage. Rat LZM which showed a single protein band on sodium dodecylsulfate polyacrylamide gel electrophoresis was purified by ion-exchange chromatography and gel filtration. The assay sensitivity of the established RIA using the purified rat LZM was 4–256 ng/ml rat LZM and was about 20 times the turbidity method. The concentration of LZM in normal rat urine was 76.2±6.0 ng/ml (mean ± SE, n = 50) using the RIA. In urine containing more than 100 ng/ml LZM, a high correlation between the values determined by the RIA and those by the turbidity method was observed. However, egg white LZM, human urinary LZM and guinea pig urinary LZM were not detectable by the RIA. Using the RIA, it was ascertained that urinary LZM excretion began to increase on day 5 in rats treated with gentamicin (15 or 30 mg/kg/day sc for 17 days), during the 6–9 h period in the rats treated with mercuric chloride (1 mg/kg sc), and during the 0–3 h period in the rats treated with p-aminophenol (1 mmol/kg sc). These significant increases in LZM excretion were not detectable by the turbidity method; therefore, it was concluded that this RIA for rat LZM was very useful for detection of minor renal damage.
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  • 179
    ISSN: 1432-0738
    Keywords: Methylmercury ; Aminoacyl tRNA synthetase ; Brain ; Protein synthesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The activities of six aminoacyl-tRNA synthetase species were determined using enzyme preparations partially purified from the brains of control and methylmercury (MeHg)-treated rats. The activities of Asp-, Leu- and Tyr-tRNA synthetases were significantly reduced in the brains of MeHg-intoxicated rats, whereas those of Lysand Met-tRNA synthetases remained unchanged. In contrast, the activity of His-tRNA synthetase was significantly increased in the symptomatic phase of MeHg intoxication. The activities of these six aminoacyl-tRNA synthetases in the control brains were affected to different extents on the direct addition of MeHg to the assay system in vitro. No positive correlation was observed between the in vivo and in vitro effects of MeHg on the enzyme activities. These results indicate that the aminoacylation of tRNA is one of the actions of MeHg, which leads to inhibition of protein synthesis, and it is suggested that the syntheses of cellular proteins may be modified in different ways by MeHg, depending on their amino acid compositions.
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  • 180
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    Anatomy and embryology 178 (1988), S. 119-127 
    ISSN: 1432-0568
    Keywords: Neuronal differentiation ; Fascia dentata ; Granule cells ; GABAergic neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Golgi impregnation was used to study the dendritic differentiation of granule cells in the rat fascia dentata. The impregnated granule cells were gold-toned allowing for a fine structural study of the same identified neurons and of the input synapses onto their cell bodies and dendrites. Due to the long postnatal formation of these cells it was possible to describe a sequence of maturational stages coexisting on the same postnatal day (P5). Characteristic features of the dendritic development of granule cells were i) occurrence of varicose swellings along the dendrites, ii) growth cones on dendritic tips, iii) transient formation of basal dendrites, and iv) progressive development of dendritic spines. Incoming synapses on the differentiating granule cells were mainly found on dendritic shafts. Their membrane specializations were symmetric. At least some of these symmetric synapses were GABAergic because immunostaining of Vibratome sections from the same postnatal stage (P5) demonstrated a well-developed GABAergic axon plexus in the fascia dentata (antibodies against glutamate decarboxylase (GAD), the GABA synthesizing enzyme). Electron microscopy of the immunostained axon plexus revealed numerous GABAergic terminals that formed symmetric synaptic contacts, mainly on shafts of differentiating dendrites but also on cell bodies of granule cells. Our results thus indicate that the plexus of inhibitory GABAergic axons is already well developed at a stage when the target neurons, the granule cells, are still being formed.
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  • 181
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    Anatomy and embryology 178 (1988), S. 155-159 
    ISSN: 1432-0568
    Keywords: Interhemispheric pathway ; Congenital anophthalmia ; Visual cortex ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an effort to assess the innate capacity of the central visual system to specify corticocortical connectivity in the absence of retinal afferents, we examined the tangential distribution of callosal cells and terminations in posterior neocortex of congenitally anophthalmic rats. Although our results indicate that the callosal pattern is clearly anomalous in these rats, all features of the normal visual callosal pattern are recognizable in mutant rats, indicating that central visual pathways can generate many aspects of normal interhemispheric connectivity in the absence of input from the periphery. On the other hand, the presence of anomalies in the pattern indicates that the eyes are necessary to finetune the distribution of callosal connections at some developemental stage. Moreover, the fact that abnormalities in the callosal pattern of mutant rats are the same as those previusly described in rats enucleated at birth suggests that the eyes begin to exert their influence on callosal development after birth.
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  • 182
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    Anatomy and embryology 179 (1988), S. 89-96 
    ISSN: 1432-0568
    Keywords: Tendon ; Myotendinous junction ; Fibroblast ; Muscle overloading ; Hypertrophy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Overloading of rat plantaris muscles was produced by aseptic ablation of the synergists. The morphological changes occurring after 1 or 2 weeks were investigated at the light and electron microscopical level in the distal tendon of the plantaris and at the myotendinous junction. Sham-operated rats were prepared as controls. In the tendon, quiescent fibrocytes were replaced by activated fibroblasts displaying a vesicular nucleus with prominent nucleoli and an outstanding increase in cytomembranes, particularly the rough endoplasmic reticulum and the Golgi complex. The plasmalemma of the fibroblasts was modified by the presence of caveolae and the surbsurface cytoplasm contained many membrane-bound vacuoles. In the tendon, the collagen bundles were disrupted, resulting in the formation of empty longitudinally oriented spaces; in these spaces, as in the pericapillary areas, no inflammatory cells were observed. At the myotendinous junction, fibroblast activation was consistently observed in both control and overloaded specimens. At this level, the sarcolemma of the finger-like projections of muscle fibres presented many caveolae close to clusters of large subsurface vacuoles. These observations indicate that, at the beginning of the compensatory hypertrophy, the adaptative changes to overloading include a non-inflammatory reaction of the tendon characterized by enhanced collagen synthesis and intensive membrane renewal and recycling. From the mechanical point of view this reaction can impair the tendon resistance to stretch. At the myotendinous junction the increased membrane turnover of the sarcolemma and the fibroblast activation can be considered permanent phenomena consequent to the increased stress exerted upon the interface connecting the contractile apparatus to the stroma.
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  • 183
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    Anatomy and embryology 179 (1988), S. 109-127 
    ISSN: 1432-0568
    Keywords: Rat ; Inferior olive ; GABA ; Glutamate decarboxylase ; Cerebellar circuitry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Boutons presumed to use γ-aminobutyric acid as neurotransmitter (GABAergic boutons) were detected by glutamate decarboxylase (GAD) immunocytochemistry in all regions of the rat inferior olive. The remarkably high concentration of these boutons allowed a clear visualization of olivary subnuclei boundaries. Regional variations in GAD immunostaining intensity were observed within the nuclear complex and were graded both visually and photometrically. The regional staining variations, for the most part, followed subnuclei boundaries and olivary zonal compartments that have been delineated by the topography of climbing fiber projections. Some subnuclei were grouped by similar staining intensities. The beta nucleus and a medial region in the ventral fold of the dorsal accessory olive were most intensely immunostained, followed by the subnucleus c of the medial accessory olive. Lower staining intensities were observed in the dorsomedial cell column, the dorsal fold of the dorsal accessory olive and the dorsal cap. The lowest intensities were observed in the subnuclei a and b of the medial accessory olive, the ventrolateral outgrowth, the rostral lamella of the medial accessory olive, the principal olive, and the lateral part of the ventral fold of the dorsal accessory olive. The factors contributing to the variations in immunostaining intensity (bouton size and frequency of occurrence) were investigated. The largest boutons were observed in the beta nucleus. Intermediate sized boutons were observed in the dorsomedial cell column, dorsal cap and the dorsal fold of the dorsal accessory olive. The smallest boutons were present in the remaining regions of the inferior olive, including the principal olive, the rostral lamella of the medial accessory olive, and the ventral fold of the dorsal accessory olive. The medial region of the dorsal accessory olive ventral fold contained a higher density of GABAergic boutons than other regions. GABAergic bouton size and innervation density therefore largely accounted for the variations in GAD immunostaining intensity. This study provides a map of the rat inferior olive based on the distribution of GABAergic nerve terminals, and may serve as a basis for characterizing different GABAergic afferent systems in the inferior olive.
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  • 184
    ISSN: 1432-0568
    Keywords: Primary afferents ; Muscle ; Anterograde tracing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The sternomastoid muscle of the rat is divided into a white (dominated by fast-glycolytic twitch fibers) and a red (dominated by fast oxidative-glycolytic twitch fibers, but also containing slow-oxidative twitch fibers) compartent. Previous reports on exclusive location of muscle spindles in the red portion were confirmed. On the basis of anterograde labeling with horseradish peroxidase-wheat germ agglutinine conjugate (WGA-HRP) it was shown in this study that, in addition to muscle spindle compartmentalisation, there was also an exclusive occurrence of tendon organs in the red part of the muscle; moreover, fine afferents (III- and IV-afferents) were mainly distributed to this portion as well. Radioimmunassay studies revealed that this part of the muscle contained twice as much substance P as the white part. It could be shown by acetylcholinesterase (AChE) histochemistry that the myelinated fibers of the white branch to the muscle exclusively displayed high enzyme activity which is characteristic for motor fibers; on the other hand, in the branch to the red portion two classes of AChE-positive fibers were found: a large one with a peak in the alpha-range, and a small one with a peak in the gammarange. In addition, there was also a group of enzyme-negative (sensory) fibers. These results also indicate the red portion of the sternomastoid muscle to be its “sensory compartment”.
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  • 185
    ISSN: 1432-0568
    Keywords: LHRH ; Rat ; Maturation ; Sex-difference
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Luteinizing hormone-releasing hormone (LHRH) neurons were immunohistochemically studied in rats of both sexes at peripubertal ages. The number of immunoreactive LHRH neurons (irLHRH neurons) was counted in the brain region from the level of the septumpreoptic area to the level of the rostral part of the infundibulum in colchicine-treated male and female rats at 30 and 60 days of age. At 30 days, irLHRH neurons were more numerous in male rats than females. At 60 days, the number of irLHRH neurons in female rats increased to the level of male rats of the same age. In non-colchicine-treated rats, the count of irLHRH neuron was quite low. The difference in the number of irLHRH neurons between colchicine-treated and non-treated rats may be regarded as the activity of LHRH system. The difference in the number of irLHRH neurons was larger in male rats than in female rats at 30 days of age. On the contrary, at 60 days of age, the difference was larger in females than in males. LHRH contents were measured in the preoptic-anterior hypothalamic area (POA-AH), where LHRH neuronal perikarya are mainly located, and in the mid-hypothalamic area. LHRH content of the POA-AH in male rats at 60 days of age was not significantly different from that at 30 days of age. While, LHRH content in the POA-AH was greater in 60-day-old female rats at proestrous morning than that in 30-day-old females. At 30 days of age, male rats tended to contain more LHRH in the POA-AH than female rats. However, either at 30 days or at 60 days, no statistically significant differences were detected between male and female rats. In mid-hypothalamic area, LHRH content in 60-day-old male rats was greater than that in 30-day-old male rats. On the other hand, there was no difference in LHRH content between 30-day-old and 60-day-old female rats. At 60 days of age, LHRH content in male rats was greater than that in female rats. The present morphological findings and LHRH measurements suggest that the functional maturation of LHRH system occurred earlier in male rats than in female rats.
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  • 186
    ISSN: 1432-0568
    Keywords: Pancreatic islet ; Insulin ; Glucagon ; Ontogeny ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ontogenetic appearances of glucagon, insulin and tyrosine hydroxylase (TH) were immunohistochemically investigated on developing pancreatic islets of rats. Glucagon immunoreactivity appeared first in some epithelial cells (g-cells) of the dorsal anlage of the pancreas on day 11.5 of gestation. On day 12.5, g-cells increased in number manufacturing the primitive islets, in which some cells appeared to be immunoreactive for insulin (i-cells) and about 40% of g-cells indicated also a slight immunoreactivity for insulin (g/i-cells). Afterwards, all the islet cells, especially g-cells, increased in number, and almost half of g-cells were g/i-cells. After day 16.5 of gestation, numerical increase of the cells with insulin immunoreactivity exceeded that of the cells with glucagon immunoreactivity, and about one fifth of g-cells were g/i-cells. After 20.5 days, however, no g/i cells were found. On day 16.5 of gestation, the immunoreactivity for TH appeared in occasional cells of the islets, but the cells did not show immunoreactivity for glucagon or insulin. It is concluded that the progenitor cells of the pancreatic islets appear to synthesize both glucagon and insulin by day 20.5 of gestation, but differentiate giving rise to mature A and B cells of adult isoets afterward.
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  • 187
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    Anatomy and embryology 178 (1988), S. 381-388 
    ISSN: 1432-0568
    Keywords: Ciliary necklaces ; Olfactory ; Vomeronasal ; Respiratory ; Development ; Freeze-fracturing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Many cilium types have at their proximal base a particulated membrane structure, the so-called ciliary necklace. Necklaces of primary and secondary cilia of olfactory receptor cells and ciliated respiratory cells, and of primary cilia of olfactory supporting cells were studied as a function of embryonic age. Strand numbers in necklaces of primary cilia of these cell types do not differ, but they differ significantly from those of necklaces of secondary cilia. Primary cilia have 2 to 4, but most commonly 3, necklace strands. This is true for necklaces of primary cilia of 8 different nasal cell types: olfactory epithelial basal and glandular cells, vomeronasal receptor and supporting cells, and microvillous respiratory epithelial cells, in addition to the 3 cell types mentioned above. Comparison with other systems suggests that primary cilia resemble flagella of eukaryotic flagellates and spermatozoa of some invertebrates with respect to their number of necklace strands. Average numbers of necklace strands in secondary olfactory cilia increase from 3–4 at the 16th and 17th gestational days to 6–7 in adults. Those in secondary respiratory cilia increase from 2–3 at the 18th and 19th gestational days to 5–6 in adults. Longer cilia have more strands than shorter ones. Necklaces often have free strand endings, also in primary cilia, suggesting that they spiral. Comparing the present data with those in the literature suggests that necklace features occurring during reciliation differ from those of de novo ciliogenesis. Primary and secondary cilia share the following qualities: 1) Membrane regions above necklace strands can differ quite drastically from those below the strands. 2) Necklace particles are firmly associated with cytoskeletal elements underneath the ciliary membrane. Hence, necklaces in primary cilia and in developing and mature secondary cilia may, together with the cytoskeleton underneath the membrane, provide a barrier for lateral diffusion and a region of membrane attachment. The latter may help to determine the shape of cilia.
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  • 188
    ISSN: 1432-0568
    Keywords: Rat ; Development ; Diencephalon ; Neuromeres ; Sulcus limitans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphogenesis of the ventricular surface of the diencephalon of the rat was studied using scanning electron microscopy, cryostat serial sections and direct observations under a dissection microscope. Based on these observations a description is given of the neuromeres present within the prosencephalon and of the termination of the sulcus limitans. Two conclusions are reached. First, three neuromeres are present in the prosencephalon. Neuromere I consists of the telencephalon, the hypothalamic regions and the parencephalon anterius. Neuromere II is the parencephalon posterius, neuromere III the synencephalon. Second, the sulcus limitans terminates ventrally in the parencephalon posterius and does not continue towards the preoptic recess. No exact termination point of the sulcus limitans could be delineated.
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  • 189
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    Acta neuropathologica 76 (1988), S. 253-264 
    ISSN: 1432-0533
    Keywords: Cerebral ischemia ; Rat ; Hyperglycemia ; Postischemic seizures ; Substantia nigra
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study explores how hyperglycemia and enhanced tissue lactic acidosis influence the density and distribution of ischemic brain damage. Ischemia of 10-min duration was produced in glucose-infused rats by bilateral carotid clamping combined with hypotension, and the brains were perfusion-fixed with formaldehyde following recirculation of 3, 6, 12 and 18 h. After about 24 h the hyperglycemic animals developed seizures, and at that time two groups were added, one fixed prior to, and one after the onset of seizures. Similar experiments were made on normoglycemic animals with recirculation times of 1.5 to 96 h. After fixation the brains were embedded in paraffin, subserially sectioned and stained with celestine blue/acid fuchsin. In both normo- and hyperglycemic animals, neurons in the dentate hilus of the hippocampal formation and in the thalamic lateral reticular nucleus showed early and dense neuronal necrosis. In neocortex, hippocampal CA1 sector and caudoputamen, hyperglycemia shortened the delay before damage occurred and markedly enhanced the damage. Specific for the hyperglycemic animals was damage of the substantia nigra, pars reticulata (SNPR), manifest already at the earliest recovery periods studied; this finding is discussed in relationship to the role SNPR is assumed to play in preventing spread of seizure discharge.
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  • 190
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    Anatomy and embryology 177 (1988), S. 349-352 
    ISSN: 1432-0568
    Keywords: Pineal body ; Mongolian gerbil (Meriones unguiculatus) ; Rat ; Calbindin D-28K (vitamin D-dependent calcium binding protein) ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunocytochemical reaction for demonstration of calbindin D-28K has been performed in superficial pineal bodies of the Mongolian gerbil (Meriones unguiculatus) and the rat. Whereas in the Mongolian gerbil there were no clearly expressed calbindin immunoreactive cells, these were numerous in the rat pineal body. Here the calbindin-positive cells — probably pinealocytes — were disposed along capillaries. In view of the role of calbindin in binding and transporting calcium and regulating its intracellular levels, the absence of this protein in the gerbil pineal body has been interpreted as signifying the inability of pinealocytes to eliminate intracellular calcium with possible consequent formation of acervuli.
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  • 191
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    Anatomy and embryology 178 (1988), S. 175-181 
    ISSN: 1432-0568
    Keywords: Liver development ; Adrenergic innervation ; Enzymic zonation ; Rat ; Spiny mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of noradrenergic innervation of rat liver was studied with a polyclonal antiserum against noradrenaline. Nerves are first seen in the larger portal vessels at day 1 after birth and reach their final distribution at 5 days after birth i.e. at the same time as the establishment of the acinar architecture and the heterogeneous distribution of NH3-metabolizing enzymes. The latter distribution of nerves is already seen at birth in the liver of the closely related but precocial spiny mouse. This shows that the onset of extrinsic sympathetic innervation is regulated by the developmental stage of the animal rather than by adaptation to extrauterine life. Chemical sympathectomy at birth with 6-hydroxydopamine did not eliminate the developmental appearance of heterogeneous distributions of NH3-metabolizing enzymes.
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  • 192
    ISSN: 1432-0568
    Keywords: Visual cortex ; VIP ; Neuronal types ; Axonal branching ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vasoactive intestinal polypeptide (VIP)-immunoreactive cells in the primary visual cortex of the rat were classified on the basis of ramification pattern of cell processes. The distribution of cells over cortical layers, and proportions of cell classes relative to total cell numbers were evaluated by means of quantitative methods. Two main types of VIP-positive neurons, the bipolar and the multipolar were distinguished constituting 76% and 24% of the VIP populations, respectively. The axons of vertically oriented bipolars were observed to ramify within a column around the descending dendrite. By contrast, multipolar cells have a non-oriented ramification pattern. The two overlapping axonal systems form the VIP-innervation of the rat visual cortex.
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  • 193
    ISSN: 1432-0568
    Keywords: Visual cortex ; VIP ; Synapse ; Spatial distribution ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the rat visual cortex vasoactive intestinal polypeptide (VIP)-containing structures were studied by means of light and electron microscopy and image analysis. VIP-immunoreactive axon terminals were found to form symmetric synapses with small dendritic shafts, dendritic spines and somata of pyramidal cells and interneurons. VIP-terminals often occured in pairs with VIP-negative, asymmetric synapses on the same postsynaptic structure. VIP-immunostained dendrites and perikarya were contacted by a purely asymmetric and a mixed population of VIP-negative terminals, respectively. Synaptic connections between two VIP-neurons are seldom as compared to the other types of VIP-synapses. Quantitative studies obtained by the image analysis of VIP-stained boutons and dendritic particles in light microscopic preparations suggest a distinct laminar distribution. Dendritic particles are most frequent in layers I–II, whereas axonal boutons have three laminar accumulations: at the border of layers I–II, in layer IV and layer VI. Together with previous results, the present findings argue for a non-random spatial distribution of VIP-boutons.
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  • 194
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    Anatomy and embryology 178 (1988), S. 309-326 
    ISSN: 1432-0568
    Keywords: Axons ; Cilia ; Microvilli ; Olfactory ; Respiratory ; Development ; Freeze-fracturing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Olfactory axons and apical structures of olfactory epithelia and of nasal respiratory epithelia of rat embryos were studied with the freeze-fracture technique; adult tissue samples of the same sources were used for comparison. At the onset of epithelial differentiation (14th gestational day) intramembranous particle densities are the same for all structures in both epithelial types. During further development, particle densities in membranes of primary cilia remain lower than those in membranes of other apical structures. Otherwise, I found the following from the 14th to the 19th day of gestation.a. Olfactory receptor cells of embryos of all age groups have axons wherein the membrane particle densities are about half those of adults. These densities are always lower than those of dendritic ending structures. Dendritic endings with primary cilia have lower densities than endings with secondary cilia; densities mainly increase when the endings sprout secondary cilia. Adult values are reached at the 18th day of gestation.b. Olfactory supporting cells with only globular particles in their apices gradually transform into, or are replaced by, supporting cells which also have dumbbell-shaped particles in their apices. Particle densities are always higher in apical structures of supporting cells than in apical structures of receptor cells. Adult values are reached at the 17th day of gestation.c. Putative ciliated and ciliated respiratory epithelial cells have considerably lower particle densities in membranes of their apical structures than do olfactory epithelial cells. Of special interest is that this is also true for secondary respiratory and olfactory cilia; as soon as genesis of secondary cilia in either epithelial type begins, their membrane features differ. Also, in contrast to apical structures of the olfactory epithelium, particle densities in apical structures of the respiratory epithelium do not systematically change during pre-natal development, and resemble the density values of adults. An exception are the microvilli of the respiratory cells with secondary cilia, membranes of which have considerably higher particle densities in adults than in embryos. In conclusion: Transformations of olfactory receptor cell dendritic endings with primary cilia into endings with secondary cilia, and of olfactory supporting cells with globular particles in their apices into cells with dumbbell-shaped particles in their apices are accompanied by increases in the densities of their intramembranous particles. These developmental changes parallel the electrophysiological onset of olfactory receptor cell specificity.
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  • 195
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    Anatomy and embryology 177 (1988), S. 267-275 
    ISSN: 1432-0568
    Keywords: Septal nuclei ; Prenatal development ; Quantitative histology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Prenatal development of septal cell groups was studied in the rat on samples taken daily from the 14th day of gestation until birth. Coronal serial sections of brains were prepared in which the topography coordinates of septal nuclei were determined, their section profiles measured and their volumes calculated. The rat septum begins to develop on embryonic days 14–15. First the individual neurons start to differentiate, then cell groups characteristic for the adult are formed between days 14 and 17, which is followed by the delineation of nuclei. The only exception is the anterior subdivision of the lateral septal nucleus where the formation of the nucleus precedes the differentiation of its constituent cells. The individual nuclei start to develop at different times defined by a medio-lateral gradient of cell migration. By embryonic day 20 the formation of the nuclei can be considered as complete: all septal nuclei and their subdivisions are to be recognized and distinguished from each other.
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  • 196
    ISSN: 1432-0568
    Keywords: Atrial specific granule ; Atrial natriuretic polypeptide ; Impulse conducting system ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was performed to clarify the distribution of ANP-containing cells in the adult rat heart by immunostaining for ANP using antiserum against α-human ANP. ANP-immunoreactive cells were generally present in the atrial walls except for the sinoatrial node. In the ventricular walls, they were distributed in the impulse conducting system, particularly the left bundle branch, Purkinje fibers on the left side of the interventricular septum, and those in the false tendons in the left ventricle, while they were sporadically seen in the atrioventricular node and bundle of His. The immunoreactive cells contained specific granules that were positive for ANP. These findings demonstrate that ANP-containing cells are present in the atrial and ventricular walls.
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  • 197
    ISSN: 1432-0568
    Keywords: Immunohistochemistry ; Choline acetyltransferase ; Olfactory bulb ; Modified glomerular complex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The main and accessory olfactory bulbs (MOB and AOB) of the rat were immunohistochemically stained with a monoclonal antibody against choline acetyltransferase (ChAT) in order to know the difference in the distribution patterns of cholinergic fibers between these two structures. A few ChAT-immunoreactive cell bodies were found in the superficial and middle parts of the external plexiform layer (EPL) of the MOB, in the granule cell layer (GCL) of the MOB, and in the GCL of the AOB. The frequency in appearance of these cells was 0.9 cells/section in the MOB and 0.3 cells/section in the AOB. While the glomerular layer (GL) and the superficial part of the EPL were most densely innervated in the MOB, the internal plexiform layer received the richest innervation in the AOB. There were no immunoreactive structures in the olfactory nerve layer of the MOB and in the vomeronasal nerve layer and glomerular layer of the AOB. In addition to a relatively homogenous distribution of cholinergic fibers in the MOB and AOB, there were several foci of very dense network of immunoreactive fibers at the posterior level of the OB. These foci formed a part of the modified glomerular complex that was recently identified using 2-deoxyglucose method and was presumed to be related to suckling behaviour in the neonatal rat.
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  • 198
    ISSN: 1432-0983
    Keywords: Ribosomal protein ; Immunological homology ; Yeast ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Polyclonal antibodies raised against ribosomal protein (r-protein) L2 of Schizosaccharomyces pombe were used to check for cross-reaktions with total r-proteins of rat liver. Using this procedure, the rat liver r-proteins, L4 and L24, were identified as being immunologically related to yeast L2. In addtional, homologies between rat liver L4 and L24 were detected. The possible implications for the regulation of r-protein synthesis are discussed.
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  • 199
    ISSN: 1432-0738
    Keywords: Acyclovir ; Embryotoxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Following three s.c. injections of acyclovir (100 mg acyclovir/kg) into rats on day 10 of pregnancy 19 litters were evaluated on day 21 of gestation and the effects were compared to the results obtained from controls (nine litters) which received the vehicle (0.1 N NaOH) only. The following results were obtained (treated group versus control group): 1) Implantations/litter: 11.2±1.3 versus 10.2±1.1; 2) resorptions/implantations: 27.7% versus 2.2%; 3) number of viable fetuses evaluated: 154 versus 90; 4) fetuses with anomalies of the skull: 78% versus 12%; 5) fetuses with anomalies of the vertebral column: 38% versus 13%; 6) gross-structural anomalies predominantly affected the skull and tail. The most frequently registered defects were: os tympanicum (smaller): 23%, os tympanicum (missing): 23%; missing tail: 7%; protruding tongue (15%); none of these defects were seen in the control fetuses. Postnatally we observed a high mortality rate among the offspring. From a total of 85 newborn (nine litters) we obtained 73 viable offspring (9.1±3.4); 81% of them had tail alterations. In the control group of eight litters (9.4±2.3) no tail alterations occurred. On day 21 postnatally 40 viable offspring were alive (mortality rate: 38.8%). Nearly all of these animals had visible alterations at multiple sites of their bodies; most frequently observed were: tail impairment, closed eyes, dragging hind-limbs, and urogenital alterations (e.g. testicular atrophy). These studies show for the first time that prenatal treatment with acyclovir induces gross-structural defects which persist postnatally. With the usually applied precautions during therapeutic use in pregnant women, the teratogenic potency of acyclovir seems to be small; however, acyclovir does have a teratogenic potential.
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  • 200
    ISSN: 1432-0738
    Keywords: Adriamycin ; Heart ; Kidney ; Liver ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of chronic adriamycin treatment on cellular defence mechanisms against free radicals has been determined in rats. To that end, the changes in vitamin E content, activity of superoxide dismutase, catalase and factors of the glutathione system were measured in heart, kidneys and liver after 24 and 52 days of treatment. Moreover, damage was assessed by measuring the activity of NADPH- and NADH-cytochrome c reductase. The results concerning the components of the oxidative defence systems in male rats showed reductions in the activity of superoxide dismutase and catalase in renal tissue and in factors of the glutathione system in liver tissue. In cardiac tissue an increased activity of catalase and elevated content of total glutathione were found. Vitamin E content was increased in liver and to a lesser extent, in kidneys. The activity of Se-dependent glutathione peroxidase sharply decreased only in liver. Major differences between male and female rats were not observed in renal and cardiac tissue, as far as protective factors were concerned. However, a decrease in catalase activity was detectable earlier in male kidneys. The protective factors in liver of female rats were far less susceptible to in vivo treatment with adriamycin, as compared to liver of male rats. Decreased activity of the cytochrome reductases was found in liver of male rats. In male renal tissue only cytochrome c reductase activity was significantly reduced. Male cardiac tissue showed no signs of biochemical damage, although from histological examination in a parallel study [J Natl Cancer Inst 76: 299–307 (1986)] lesions were evident. In female rats no damage was found in liver, kidneys and heart.
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