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  • 1
    Electronic Resource
    Electronic Resource
    Investigations of cardiovascular 5-hydroxytryptamine receptor subtypes in the rat (1988)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 1-8 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169468
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  • 2
    Electronic Resource
    Electronic Resource
    Stimulation of central alpha-2 adrenoceptors inhibits gastric secretion in rats by releasing vasopressin (1988)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 164-168 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169244
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  • 3
    Electronic Resource
    Electronic Resource
    Actions of calcitonin gene-related peptide and tachykinins in relation to the contractile effects of capsaicin in the guinea-pig and rat heart in vitro (1988)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 649-655 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175791
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  • 4
    Electronic Resource
    Electronic Resource
    Immunological homologies between yeast ribosomal protein L2 and rat liver ribosomal proteins L4 and L24 (1988)
    Springer
    Current genetics 13 (1988), S. 235-239 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00387769
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  • 5
    Electronic Resource
    Electronic Resource
    Protective effect of stimulated splenic transplants against rodent malaria — preliminary results (1988)
    Springer
    Pediatric surgery international 3 (1988), S. 338-342 
    Details
    ISSN: 1437-9813
    Keywords: Spleen ; Autotransplantation ; Protective function ; Malaria ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Autologous splenic fragments regenerate after transplantation. The regenerated mass only attains a small proportion of that of the normal spleen. Some data on the protective function are controversial. Malaria parasites were inoculated to test splenic function in rats. Peak parasitemia, the course of parasitemia, and anemia were comparable in normal and autotransplanted rats. In rats with splenic transplants only the duration of the parasitemia was longer than in normal rats. In contrast, splenectomized rats were unable to clear the parasites from the blood and became progressively anemic. After stimulating regeneration by increasing the work load to the white pulp or the macrophage system, more regenerated tissue was found, but the protective function did not increase. The amount of regenerated splenic tissue does not correlate with its protective function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00189172
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  • 6
    Electronic Resource
    Electronic Resource
    Morphological and biological characteristics of mammary tumours induced by the direct application of DMBA powder to rat mammary glands (1988)
    Springer
    Virchows Archiv 414 (1988), S. 1-7 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00749731
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  • 7
    Electronic Resource
    Electronic Resource
    Epithelial restitution in the large intestine of the rat following insult with bile salts (1988)
    Springer
    Virchows Archiv 414 (1988), S. 77-81 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00749741
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  • 8
    Electronic Resource
    Electronic Resource
    Laser welded vascular anastomosis (1988)
    Springer
    Urological research 16 (1988), S. 127-131 
    Details
    ISSN: 1434-0879
    Keywords: Microsurgery ; CO2 laser ; Neodymium Yag laser ; Vascular anastomosis ; Rat ; Tensile strength ; Histology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A comparative study was undertaken to investigate the application of a specially adapted microsurgical Neodymium Yag Laser system with a wavelength of 1,319 μm and a CO2 laser system for laser assisted microvascular end-to-end anastomosis (LAMA) of the rat femoral artery. Conventionally sutured anastomoses served as controls. Postoperative investigations included patency tests, light microscopy and tensile strength measurements. Both laser systems seem to be equally suitable for LAMA: The patency rates do not differ from those of sutured anstomoses and formation of microscopically small aneurysms occurred predominantly in control animals and only once in laser groups. The clamp time needed for LAMA was half the time that was needed for sutured anastomoses. Wound healing in all groups was similar with less fibrotic reactions and less foreign body granulomas in laser groups. At all intervals tensile strength was significantly higher for sutured anastomoses while differences between the CO2- and the ND: Yag-laser groups were not statistically significant. Potential applications in urology include microvascular anastomoses in erectile dysfunction, pediatric and reconstructive urology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00261970
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  • 9
    Electronic Resource
    Electronic Resource
    Somatostatin-gastrin interactions in the rat stomach (1988)
    Springer
    Research in experimental medicine 188 (1988), S. 115-121 
    Details
    ISSN: 1433-8580
    Keywords: Gastrin ; Rat ; Somatostatin ; Stomach
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Low concentrations of somatostatin and gastrin within or slightly above the range of physiologically circulating levels were perfused in the isolated, vascularly perfused rat stomach preparation. Somatostatin at 10 and 50 pg/ml significantly inhibited acetylcholine-stimulated gastrin secretion by 26% and 45%, respectively, whereas perfusion of 50 and 500 pg/ml exogenous gastrin did not modify gastric somatostatin secretion. Perfusion of somatostatin-antiserum significantly increased gastrin release by 235%. It is concluded that (1) somatostatin is a powerful inhibitor of the gastrin cell under in vitro conditions; the data are in accordance with a concept that endogenous somatostatin could act as a true hormone; (2) the secretory activity of the somatostatin cell is not significantly affected by circulating gastrin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01852267
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  • 10
    Electronic Resource
    Electronic Resource
    Malaria infection in rats with stimulated splenic red pulp: The blood flow and protective effect in normal and transplanted splenic tissue (1988)
    Springer
    Research in experimental medicine 188 (1988), S. 267-276 
    Details
    ISSN: 1433-8580
    Keywords: Splenic autotransplantation ; Phenylhydrazine ; Malaria infection ; Rat ; Blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After splenic autotransplantation both weight and blood flow of the regenerated splenic tissue are decreased. In addition, the protective function of the transplant is less compared to that of the normal spleen. In the present study, the red pulp of normal and transplanted splenic tissue was stimulated by injections of phenylhydrazine to increase the weight, the blood flow, and the protective function. After stimulation, the weight of the normal spleen increased to 900 ± 70 mg (control 530 ± 20 mg) and the transplanted tissue to 240 ± 70 mg (control 70 ± 20 mg). This enlargement was caused by an increase in the splenic red pulp. However, the relative blood flow decreased in both the normal spleen and the transplant to 50% of the normal value. To evaluate the protective function of the stimulated splenic tissue, normal, splenectomized and transplanted rats were infected withPlasmodium berghei. Despite the dramatic increase in the red pulp, neither the normal nor the transplanted animals showed a survival rate superior to that of the splenectomized animals. The mass of splenic tissue obviously does not correlate with the protective effect of the spleen in parasitic infections.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01852275
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  • 11
    Electronic Resource
    Electronic Resource
    Failure to prolong rat renal allograft survival time by photochemical donor kidney pretreatment during hypothermic pulsatile kidney preservation (1988)
    Springer
    Urological research 16 (1988), S. 53-55 
    Details
    ISSN: 1434-0879
    Keywords: Renal transplantation ; Rat ; Ultraviolet irradiation ; PUVA ; Pulsatile perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Systemic photochemical pretreatment of a rat kidney donor with the photosensitizer 8-methoxypsoralen (8-MOP; 0.06 mg/kg intravenously, 10 min before graft removal) plus ex vivo longwave ultraviolet (UVA) irradiation of the kidney graft during simple hypothermic storage significantly prolonged survival time in allogeneic recipients. In contrast to these results, the present use of UVA irradiation during hypothermic pulsatile kidney perfusion using Euro-Collins® solution containing 8-MOP (0.06 mg/ml) did not prolong graft survival compared with untreated controls. Systemic application of 8-MOP to the kidney donor may be necessary for effective action of the combined photochemical treatment as a method of immunoalteration. The extended UVA irradiation time and the local use of 8-MOP in the preservation fluid had no effect on graft survival possibly because of inadequate tissue distribution of 8-MOP during both hypothermia and perfusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00264629
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  • 12
    Electronic Resource
    Electronic Resource
    Comparison of long-term and short-term stretch on rat urinary bladder in vitro (1988)
    Springer
    Urological research 16 (1988), S. 277-280 
    Details
    ISSN: 1434-0879
    Keywords: Electrical stimulation ; Stretching ; Time factor ; Bladder strip ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Distension of the human urinary bladder often causes prolonged impairment of its function. To investigate the effects of the duration of stretch on bladder smooth muscle the active length-tension relation, electrically evoked, was described in rat detrusor strips during a short-term and a long-term stretch. The amplitude of active tension increased at first and then decreased abruptly at greater stretch lengths, the maximum being at muscle lengths 230–250% (100%=resting length) in both types of stretches. When the strips had been at maximum length (300%) for three hours the amplitude was significantly decreased during release as compared to the amplitude found during stretch to the maximum length at comparable lengths. If the strips were released immediately from the maximum length the amplitude responded in an opposite manner. Therefore we conclude that the duration of stretching of bladder smooth muscle significantly affects its mechanical activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00263635
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  • 13
    Electronic Resource
    Electronic Resource
    Intestinal ammonium production in the rat: The role of the colon, small intestine, and circulating glutamine (1988)
    Springer
    Research in experimental medicine 188 (1988), S. 1-7 
    Details
    ISSN: 1433-8580
    Keywords: Rat ; Intestinal ammoniagenesis ; Glutamine metabolism ; Small intestine ; Colon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The intestinal ammonium production and the intestinal uptake of circulating glutamine were investigated in anesthetized intact rats and rats with resected small intestine or colon by simultaneous measurements performed on portal and arterial blood. It was shown that ammonium release into the portal blood by the small intestine is of equal magnitude to that released by the colon, and that circulating glutamine participates in ammonium production by the small intestine. Increased levels of circulating glutamine induced by its i.v. infusion to intact rats were not accompanied by an increase in intestinal ammonium production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01852088
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  • 14
    Electronic Resource
    Electronic Resource
    When should treatment of acute experimental pancreatitis be started? (1988)
    Springer
    Research in experimental medicine 188 (1988), S. 123-129 
    Details
    ISSN: 1433-8580
    Keywords: Acute experimental pancreatitis ; Sodium taurocholate ; Pancreatic enzymes ; Pancreatic morphology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sodium taurocholate pancreatitis in the rat is a frequently used experimental model for evaluating therapeutical regimes in this disease. It is, however, uncertain when treatment should be started, as the early phase of this experimental model and thus the time when the pancreatitis really develops is unknown. Serum and pancreatic enzymes, as well as pancreatic morphology, were therefore studied 5, 30, and 60min after induction of sodium taurocholate pancreatitis. It was found that increase in serum enzymes and decrease in pancreatic enzymes and morphological changes characteristic for acute pancreatitis develop as early as 5 and 30 min after induction of pancreatitis. Thus, therapy in this model may be started shortly after induction of acute pancreatitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01852268
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  • 15
    Electronic Resource
    Electronic Resource
    Comparison of calbindin D-28K immunoreactivity in superficial pineal bodies of mongolian gerbil and rat (1988)
    Springer
    Anatomy and embryology 177 (1988), S. 349-352 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315843
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  • 16
    Electronic Resource
    Electronic Resource
    The distribution of atrial natriuretic polypeptide (ANP)-containing cells in the adult rat heart (1988)
    Springer
    Anatomy and embryology 177 (1988), S. 477-484 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00305135
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  • 17
    Electronic Resource
    Electronic Resource
    Morphological lesions in the brain preceding the development of postischemic seizures (1988)
    Springer
    Acta neuropathologica 76 (1988), S. 253-264 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00687772
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  • 18
    Electronic Resource
    Electronic Resource
    Ontogenetic development of septal nuclei in the rat (1988)
    Springer
    Anatomy and embryology 177 (1988), S. 267-275 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00321137
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  • 19
    Electronic Resource
    Electronic Resource
    The distribution of anterogradely labeled I–IV primary afferents in histochemically defined compartments of the rat's sternomastoid muscle (1988)
    Springer
    Anatomy and embryology 177 (1988), S. 235-243 
    Details
    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”.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00321134
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  • 20
    Electronic Resource
    Electronic Resource
    Luteinizing hormone-releasing hormone (LHRH) neurons in the male and female rats at peripubertal period (1988)
    Springer
    Anatomy and embryology 178 (1988), S. 475-480 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00305034
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    Transient coappearance of glucagon and insulin in the progenitor cells of the rat pancreatic islets (1988)
    Springer
    Anatomy and embryology 178 (1988), S. 489-497 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00305036
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    Electronic Resource
    Noradrenergic innervation of developing rat and spiny mouse liver (1988)
    Springer
    Anatomy and embryology 178 (1988), S. 175-181 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02463651
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  • 23
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    Ramification patterns of vasoactive intestinal polypeptide (VIP)-cells in the rat primary visual cortex (1988)
    Springer
    Anatomy and embryology 178 (1988), S. 197-206 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318223
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    Types and spatial distribution of vasoactive intestinal polypeptide (VIP)-containing synapses in the rat visual cortex (1988)
    Springer
    Anatomy and embryology 178 (1988), S. 207-217 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318224
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    Electronic Resource
    Pre-natal development of rat nasal epithelia (1988)
    Springer
    Anatomy and embryology 178 (1988), S. 309-326 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00698662
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    Electronic Resource
    Tendon and myo-tendinous junction in an overloaded skeletal muscle of the rat (1988)
    Springer
    Anatomy and embryology 179 (1988), S. 89-96 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00305103
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    Electronic Resource
    The rat inferior olive as seen with immunostaining for glutamate decarboxylase (1988)
    Springer
    Anatomy and embryology 179 (1988), S. 109-127 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00304693
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    Electronic Resource
    Differentiation of granule cells in relation to GABAergic neurons in the rat fascia dentata (1988)
    Springer
    Anatomy and embryology 178 (1988), S. 119-127 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02463645
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    Electronic Resource
    The pattern of callosal connections in posterior neocortex of congenitally anophthalmic rats (1988)
    Springer
    Anatomy and embryology 178 (1988), S. 155-159 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02463649
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  • 30
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    Electronic Resource
    Pre-natal development of rat nasal epithelia (1988)
    Springer
    Anatomy and embryology 178 (1988), S. 381-388 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00306044
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    Cholinergic innervation of the main and the accessory olfactory bulbs of the rat as revealed by a monoclonal antibody against choline acetyltransferase (1988)
    Springer
    Anatomy and embryology 178 (1988), S. 481-488 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00305035
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    A SEM study on the development of the ventricular surface morphology in the diencephalon of the rat (1988)
    Springer
    Anatomy and embryology 179 (1988), S. 73-80 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00305101
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    Licking during forced spout alternation in rats: resetting the pacemaker or disconnecting the motor output? (1988)
    Springer
    Experimental brain research 70 (1988), S. 561-568 
    Details
    ISSN: 1432-1106
    Keywords: Rhythmic movement ; Licking ; Motor learning ; Hypoglossal activity ; Videorecording ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats trained to alternate between two adjacent drinking spouts (each spout is retracted after a single lick and presented again after the animal has licked at the other spout) emit 2.5 licks instead of the optimum 1 lick per spout presentation. The question whether the pacemaker of licking is reset or continues to run during transition between spouts was addressed in three experiments performed in 10 highly overtrained rats. Videorecording analysis of oro-facial activities showed that the rat's mouth was firmly closed during the 500 ms transition between spouts. EEG was recorded from the region of hypoglossal nucleus with implanted bipolar electrodes during continued licking at one spout and during spout alternation. Averaging (n = 256, 1024 ms) centered around the onset of the first lick at the newly contacted spout showed 2–3 lick related potentials in the post-transitional interval whereas only one such wave occasionally appeared at the end of the pre-transition period. Computer plotted distributions of post-transition licks (timed with respect to the last pre-transition lick) were examined while the horizontal or vertical distance between spouts was increased. Growing spout separation changed the height but not the timing of the modes of the post-transition lick distribution. This phase-locked synchronization of pre- and post-transition licks indicates that the central timing network of the lick generator is not reset but continues to run during transition between spouts and that the cessation of tongue movements is due to inhibition of the intracycle pattern generator and motor output. It is concluded that more sensitive recording techniques are required to detect the activity of the central timing network in absence of overt licking.
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    URL: http://dx.doi.org/10.1007/BF00247603
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    A small population of retinal ganglion cells projecting to the retina of the other eye (1988)
    Springer
    Experimental brain research 71 (1988), S. 611-617 
    Details
    ISSN: 1432-1106
    Keywords: Retina ; Projection ; Development ; Rat ; Rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We traced the retino-retinal projection with Rhodamine B isothiocyanate (RITC), Rhodamin labelled latex microspheres (RLM), horseradish peroxidase (HRP) and choleratoxin conjugated horseradish peroxidase (BHRP). The number and distribution of ganglion cells projecting to the contralateral eye were recorded. Newborn and young rats have up to about 130 ganglion cells projecting to the other retina; this confirms previous findings. We extended these findings in two ways. First, we describe a similar projection in rabbits consisting of fewer cells; second, we describe the persistence of a small component of this projection into adulthood. In addition we show with RITC and Nuclear Yellow double tracing that some of the retino-retinal ganglion cells have an axon collateral which projects to the superior colliculus. We performed control experiments in order to exclude spillover of tracer which might produce false positive labelling.
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    URL: http://dx.doi.org/10.1007/BF00248754
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    Intrathecal galanin at low doses increases spinal reflex excitability in rats more to thermal than mechanical stimuli (1988)
    Springer
    Experimental brain research 71 (1988), S. 663-666 
    Details
    ISSN: 1432-1106
    Keywords: Galanin ; Spinal cord ; Flexor reflex ; Intrathecal ; Cutaneous afferents ; Thermoreceptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The neuropeptide galanin (GAL) was injected intrathecally (i.t.) in decerebrate, spinalized, unanesthetized rats and its effect on the nocifensive flexor reflex was examined. The reflex, which was evoked by intense mechanical or thermal stimulation of the foot, was recorded from the ipsilateral hamstring muscles. I.t. GAL increased reflex excitability significantly more to thermal than to mechanical stimuli. It is suggested that GAL, which is present in sensory fibers that innervate the skin, is released by the central terminals of cutaneous afferents that are much more sensitive to thermal than to mechanical stimuli.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00248760
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    Differential distribution of biogenic amines in the hypoglossal nucleus of the rat (1988)
    Springer
    Experimental brain research 73 (1988), S. 305-314 
    Details
    ISSN: 1432-1106
    Keywords: Hypoglossal nucleus ; Biogenic amines ; Immunocytochemistry ; Tyrosine hydroxylase ; Serotonin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of biogenic amines in the rat hypoglossal nucleus (nXII) was investigated with immunocytochemical methods using antibodies to tyrosine hydroxylase (TH) as a marker for catecholamines, and to 5-hydroxytryptamine (5-HT), the principal indoleamine, at the light microscopic level. TH and 5-HT immunoreactivity were found throughout all regions of nXII. Although the innervations overlapped, clearly differnt patterns of distribution were observed. TH immunoreactivity was localized primarily in the ventromedial quadrant of the caudal half of nXII and appeared largely as perisomatic-like profiles. In contrast, 5-HT immunoreactivity was greatest dorsally along the caudal half of nXII, although secondary foci of staining were evident ventrolaterally and, to a lesser extent, ventromedially. A perisomatic-like pattern of termination was observed for 5-HT in both dorsal and ventral regions of nXII. Since ventral and dorsal districts of nXII contain motoneurons that innervate protrusor and retrusor tongue muscles, respectively, we propose that the overlapping, yet differential distributions of catecholamines and indoleamines are important in controlling the relationships between functionally related groups of nXII motoneurons. These findings are discussed in relation to oro-lingual motor dysfunction.
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    URL: http://dx.doi.org/10.1007/BF00248222
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    In vitro regeneration of adult rat ganglion cell axons from retinal explants (1988)
    Springer
    Experimental brain research 73 (1988), S. 393-401 
    Details
    ISSN: 1432-1106
    Keywords: Rat ; Ganglion cell axons ; Regeneration ; Chemically defined media ; Fluorescent tracers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The potential for regeneration of adult rat ganglion cell (RGC) axons was investigated in vitro. Explants from RITC (rhodamine-B-isothiocyanate) retrogradely labeled and in vivo axotomized retinae were placed on dishes coated with various substrates. The retinal pieces were cultivated in a serum-free medium and incubated under 50 to 80% O2-enriched and 5% CO2-containing atmosphere. Under these conditions, massive outgrowth of fibers was observed as early as 24 h after explantation and over a period of time extending up to 7 days in culture. By various criteria, two main types of processes could be characterized: (1) Short, thick processes emerged from either migrated flat cells or from cells inside the retinal explant, and (2) long and thin processes emerged from cells in the ganglion cell layer (GCL). By immunohistochemistry, the short processes and the cells from which they had emerged, appeared to be glial acidic fibrillary protein (GFAP)-positive Thy 1 and L 1-negative, suggesting their glial nature. The second type of long, thin processes appeared to be GFAP-negative, L1- and Thy 1-positive, indicating that they were neuronal, probably RGC processes. Proof that long fibers emerged from RGCs was provided by retrograde labeling of RGCs with RITC prior to explanation. Numerous RITC-filled RGCs survived in vitro. Regrowing axons retransported part of the accumulated fluorescent dye in the orthograde direction and thus unequivocally permitted their identification as RGC axons. The fact that adult RGC axons can reelongate in vitro might provide a useful bioassay for investigations on the factors that either support or inhibit regrowth of axons from CNS neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00248232
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    Responses of nucleus reticularis tegmenti pontis neurons to vestibular stimulation in the rat (1988)
    Springer
    Experimental brain research 69 (1988), S. 417-423 
    Details
    ISSN: 1432-1106
    Keywords: Nucleus reticularis tegmenti pontis ; Vestibular ; Flocculus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Forty-nine neurons were recorded in the nucleus reticularis tegmenti pontis (NRTP) during horizontal vestibular and/or optokinetic stimulation in immobilized pigmented rats. During optokinetic stimulation, the response of NRTP neurons was either unidirectional (51%) or bidirectional (49%). Histological reconstruction showed that unidirectional neurons were located in the dorsal-medial part of NRTP, and bidirectional neurons in the lateral part. All neurons exhibited a response during pure vestibular sinusoidal stimulation in the frequency range 0.025 Hz-0.2 Hz. NRTP neurons were divided into two groups according to their threshold to vestibular stimulation. Group A neurons had a low threshold, a low spontaneous activity and their firing frequency slowly increased with acceleration. Group B neurons showed opposite characteristics. Phase and gain analysis suggested that NRTP neurons carry a head velocity signal. After hemiflocculectomy, the gain of the vestibular response of contralateral NRTP neurons increased. From these data, the role of NRTP in the horizontal vestibulo-oculomotor is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00247587
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    Electronic Resource
    Bilateral receptive fields of cells in rat Sm1 cortex (1988)
    Springer
    Experimental brain research 70 (1988), S. 155-165 
    Details
    ISSN: 1432-1106
    Keywords: Sm1 cortex ; Receptive fields ; Rat ; Bilateral receptive fields ; Hindlimb
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Single cells in the primary somatosensory (Sm1) cortex were investigated for responses to bilateral hindpaw stimulation in Wistar rats anaesthetised by continuous intravenous administration of Althesin. Fifty-one percent of cells sampled (N = 134) responded to equivalent punctate mechanical stimuli delivered to both the contralateral and ipsilateral hindpaws under light anaesthesia. The distribution by cortical depth of cells with receptive fields (RFs) on both hindpaws was not significantly different from cells which had only contralateral RFs. No cell was found with a purely ipsilateral RF. For 86% of cells tested (N=44) the ipsilateral RF was partly or completely homologous with areas within the contralateral RF. The sizes of ipsilateral RFs were smaller on 66% of occasions when tested against their contralateral RFs. Modal latencies to ipsilateral mechanical stimulation were longer than to contralateral stimulation (34.1±9.1 ms (S.D) cf. 26.4±7.2 ms, N=44). Ipsilateral RFs were lost for 77% of cells tested following a 33% increase in anaesthetic infusion rate. Conditioning mechanical stimuli applied to the centre receptive field (CRF) on the ipsilateral hindpaw reduced or abolished a cell's responses to equivalent test stimuli applied to it's contralateral CRF with C-T intervals of 20–200 ms. Conditioning stimuli applied to the CRF contralateral to the cell reduced or abolished responses to test stimuli on the cell's ipsilateral CRF using C-T intervals of 0–900 ms. Responses in one cortex to stimulation of the ipsilateral hindpaw were unaffected by elimination of responses from the same hindpaw in the opposite contralateral Sm1 cortex, where responses had been suppressed by topical Lignocaine administration. Retrograde transport of horseradish peroxidase from hindpaw Sm1 cortex labelled many cells in homolateral thalamus, but failed to label cells in the entire forebrain contralateral to the injection site. It is concluded that direct crossed thalamocortical and callosal Sm1-Sm1 pathways do not contribute to the production of hindpaw ipsilateral receptive fields.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271857
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    Electronic Resource
    Localization of isoenzymes II/III of protein kinase C in the rat visual cortex (area 17), hippocampus and dentate gyrus (1988)
    Springer
    Experimental brain research 72 (1988), S. 443-449 
    Details
    ISSN: 1432-1106
    Keywords: Protein kinase C subspecies ; Immunocytochemistry ; Visual cortex ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monoclonal antibodies against type II and type III subspecies of protein kinase C PkC(II/III) were used to map the distribution of these isoenzymes in the visual cortex (area 17), hippocampus and dentate gyrus of the rat. PkC(II/III)-immunocytochemistry resulted in a specific staining of neuropil and of neuronal somata with their proximal dendrites. The majority of immunopositive cells exhibited a punctate distribution of reaction product, while only a few neurons were homogeneously labeled. In the visual cortex stained neurons were distributed throughout all laminae and reached a particularly high density in layers II/III. Moreover, PkC(II/III)-positive neurons were found within the strata pyramidale and radiatum of the hippocampus proper and in the stratum granulosum, the subgranular zone and the hilar region of the dentate gyrus. The present results suggest that PkC(II/III)-positive neurons constitute a distinct population of both projection and local circuit neurons that are not exclusively associated with any one neurotransmitter system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00250589
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  • 41
    Electronic Resource
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    Differences in magnesium and calcium effects on N-methyl-D-aspartate- and quisqualate-induced decreases in extracellular sodium concentration in rat hippocampal slices (1988)
    Springer
    Experimental brain research 71 (1988), S. 425-430 
    Details
    ISSN: 1432-1106
    Keywords: Extracellular Na+ concentration ; Quisqualate (quis) ; N-methyl-D-aspartate (NMDA) ; Tetrodotoxin (TTX) ; Hippocampal area CA1 ; Rat ; Extracellular Ca2+ concentration ; Extracellular Mg2+ concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Decreases in extracellular sodium concentration ([Na+]o) and associated slow negative field potentials (fp's) were monitored with double barreled sodium sensitive/reference microelectrodes in area CA1 of rat hippocampal slices during iontophoretic application of the glutamate receptor agonists N-methyl-D-aspartate (NMDA) and quisqualate (quis). The effects of lowering [Ca2+]o on these signals were compared to those of lowering [Mg2+]o. Both NMDA- and quis-induced decreases in [Na+]o of up to 60 mM and in the fp's of up to 8 mV. Decreasing [Mg2+]o enhanced NMDA-induced signals, whereas quis-induced signals were unaffected. Lowering [Ca2+]o also enhanced NMDA signals, although somewhat less than lowering [Mg2+]o. This effect was still present, even when voltage dependent Na+ currents were blocked by 10-7 tetrodotoxin. Interestingly, quis-induced signals could be enhanced in a low Ca2+ medium as well, but only when high quis concentrations were used. The results suggest that, during the sorts of large decreases of [Ca2+]o observed during seizure activity, activation of NMDA receptors is facilitated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00247502
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    Topographic differences in retinal axons in the dorsal lateral geniculate nucleus of the rat: a quantitative reexamination using anterograde transport of horseradish peroxidase (1988)
    Springer
    Experimental brain research 69 (1988), S. 481-488 
    Details
    ISSN: 1432-1106
    Keywords: Dorsal lateral geniculate nucleus ; Horseradish peroxidase ; Retinal axons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Retinal endings in the dorsal lateral geniculate nucleus (dLGN) of the rat were visualized by anterogradely transported horseradish peroxidase following injections in the optic tract. The morphological findings confirm the two types of retinal axons previously suggested by Golgi investigations. In the caudal third of the dLGN type 2b axons, with small dense clusters of boutons, are the only representatives of retinal fibres seen. In the rostral two thirds they are intermingled with the larger type 2a terminals, but tend to accumulate laterally, adjacent to the optic tract. This study supports the concept that large retinal ganglion cells probably give rise to 2a axons that may represent a Y-like channel, whereas 2b axons are derived from small ganglion cells, and may relay a W-like pathway.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00247302
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    Immunocytochemical evaluation of a cholinergic-specific ganglioside antigen (Chol-1) in the central nervous system of the rat (1988)
    Springer
    Experimental brain research 72 (1988), S. 71-82 
    Details
    ISSN: 1432-1106
    Keywords: Cholinergic-specific ganglioside ; Cholinergic neurons ; Chol-1 ; Spinal cord ; Brain ; Retina ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous work from this laboratory has identified gangliosidic surface markers specific for cholinergic neurons. Antibodies to these markers, collectively designated Chol-1, induce complement-mediated lysis of the cholinergic subpopulation of synaptosomes and provide the basis for a new immunocytochemical method for staining cholinergic neurons in rat, guinea pig and human material. The specification and localization of immunocytochemical staining for Chol-1 was investigated in selected areas of the rat central nervous system. The antigen was typically expressed on all neurons previously identified as being cholinergic using monoclonal antibodies to choline acetyltransferase. At spinal levels Chol-1 was present on large and smaller cell bodies in the ventral horn motoneuron area. The preganglionic sympathetic neurons in the thoracic intermediolateral nucleus were also Chol-1-positive. Nerve terminal-like staining was observed in association with stained large Chol-1 positive and smaller unstained Chol-1 negative neurons, and in lamina I and III of the dorsal horn. In the mesencephalon, motoneurons of the oculomotor and trochlear nucleus, as well as neurons within the pedunculopontine tegmental nucleus and the red nucleus were Chol-1-positive. In addition visceromotoneurons of the Edinger-Westphal nucleus were stained with anti Chol-1 antibodies. In the basal forebrain the antibodies gave a positive reaction on well known cholinergic neurons in the vertical and horizontal limbs of the diagonal bands of Broca and the medial forebrain bundle. In agreement with studies using antibodies to choline acetyltransferase, a small sub-population of neostriatal neurons (1–2%) was Chol-1-positive. In the rat retina, both anti-Chol-1 and anti-choline acetyltransferase antibodies gave rise to a nerve terminal-like staining in the same bands within the inner plexiform layer. The anti-Chol-1 antibodies also stain normal and pathological human material and could have a useful application in human neuropathology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00248502
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    Intra-ventricular infusion of the NMDA antagonist AP5 impairs performance on a non-spatial operant DRL task in the rat (1988)
    Springer
    Experimental brain research 73 (1988), S. 181-188 
    Details
    ISSN: 1432-1106
    Keywords: AP5 ; NMDA antagonist ; Hippocampus ; DRL ; Memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were trained to lever press on a differential reinforcement of low rates (DRL-18 s) schedule. They were then allocated to four treatment groups. These were: hippocampal aspiration lesions [HIPP]; implantation of osmotic minipumps for intraventricular infusion of either (a) the NMDA receptor antagonist 30 mM D, L-2-amino-5-phosphonopentanoic acid [AP5] or (b) vehicle [VEH]; and an unoperated control group [UNOP]. In subsequent DRL testing, the HIPP group showed a profound and enduring loss of efficiency, resulting from an increased tendency to respond too early; the AP5 group showed a qualitatively similar, but less severe, impairment followed by full recovery once the minipumps had expired; the VEH and UNOP groups both maintained their pre-operative levels of efficiency. We conclude that AP5 infusion disrupts temporary memory storage in the hippocampus, and that the hippocampus is concerned with the retention of memories outside the purely spatial domain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00279671
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    Electronic Resource
    Three-dimensional reconstruction of transmitter-identified central neurons by “en bloc” immunofluorescence histochemistry and confocal scanning microscopy (1988)
    Springer
    Experimental brain research 73 (1988), S. 441-446 
    Details
    ISSN: 1432-1106
    Keywords: Neurotransmitter ; Immunohistochemistry ; 3-D reconstruction ; Confocal microscopy ; Rat ; Lamprey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A new method for three-dimensional reconstruction of transmitter-identified neurons is presented which involves “en bloc” immunofluorescence histochemistry and confocal scanning microscopy. The technique was applied to different types of neurons in the rat brain and lamprey spinal cord. Thick sections or tissue “blocs” (50–200 μm thick) were incubated with antisera against neuropeptides or monoaminergic markers, followed by fluorescent secondary antibodies. Three-dimensional reconstructions were obtained by scanning the preparations in sequential focal planes with a thin laser beam, while sampling the emitted light in each focal plane. The method is convenient and can be applied to a wide variety of neuron types. The reconstructions obtained are accurate since the “optical serial sections” of the specimen are perfectly aligned, and optic disturbances such as “halo” phenomena do not occur.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00248236
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    Electronic Resource
    Rapid effects of adult-onset hypothyroidism on dendritic spines of pyramidal cells of the rat cerebral cortex (1988)
    Springer
    Experimental brain research 73 (1988), S. 583-588 
    Details
    ISSN: 1432-1106
    Keywords: Adult hypothyroidism ; Dendritic spines ; Pyramidal cells ; Cerebral cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have previously shown (Ruiz-Marcos et al. 1980, 1982) that thyroidectomy (T) performed in rats at 40 days of age, well past the neonatal period of development, results by 80–90 days of age in a decrease of the number of spines along the shaft of pyramidal neurons with the cell body in layer V in the visual area of the cerebral cortex. We have here studied how soon after the operation an effect on spine number and distribution may be observed. We have found that the response of these neurons to T is very rapid: a decrease in the number of spines/shaft between T and age-paired controls (C) rats is statistically significant by the earliest period of observation, namely 5 days after T. These results may be related to those of Dembri et al. (1983) showing that T performed in adult rats decreases the activity of Type I RNA polymerase by 5 days after the operation. It is possible that T impairs the synthesis of some compound(s) necessary for the formation and maintenance of spines. The present results suggest that spine number is not a fixed structure of the apical shaft once brain development is over, but is in a state of continuous formation and degradation. We have further observed that the effect of T performed at 40 days of age is more pronounced in the distal part of the shaft than on the rest, a result similar to that found after neonatal T (Ruiz-Marcos et al. 1982). However, contrary to findings after early hypothyroidism, T at 40 days of age does not distort the distribution of spines along the shaft.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00406617
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    Vasopressin secretion: suppression after light and tone stimuli previously paired with footshocks in rats (1988)
    Springer
    Experimental brain research 71 (1988), S. 291-297 
    Details
    ISSN: 1432-1106
    Keywords: ACTH ; Emotional response ; Motor activity ; Vasopressin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an attempt to find whether vasopressin (VP) secretion is suppressed by learned emotional stress, we have given rats under a hypertonic condition simultaneously applied light and tone that had been paired previously with footshocks and have quantified immunoreactive VP (ir-VP) in the plasma. In a training session light (60 watt) and tone (2 kz) of 3-s duration which were paired with electric footshocks (50 Hz, 1-s duration) were given to rats 11 times at an interval of 30 s. Various lengths of time after the training, the rats were tested with light and tone, which were unpaired with footshocks and repeatedly applied every 15 s for 3 min in the box used for training. Hypertonic NaCl (0.5 M, 2 ml/ 100 g b. w.) was injected s. c. 30 min before testing to increase the basal level of plasma VP. After testing, plasma ir-VP was significantly less in the experimental group than in the 0-mA control group of rats that were trained without FS. The values for the experimental group were also significantly less than those of untested control rats that had been trained with FS but were not tested. Plasma osmolality and blood haemoglobin concentration were not significantly different between control and experimental groups. Plasma immunoreactive adrenocorticotrophic hormone (ir-ACTH) level was higher and motor activity as expressed by cumulative time period of body movement during testing was lower in the experimental group than in either of the control groups. The difference in plasma ir-VP between experimental and control groups was statistically significant two days but not seven days after training, whereas ACTH and motor activity in experimental groups were still significantly different from those in control groups seven days after training. The suppressive VP and augmentative ACTH responses to testing disappeared in the rats that had received light and tone repeatedly during the intervening period between training and testing. These data support the hypothesis that emotional stimuli suppress VP secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00247489
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    Epilepsy and electromagnetic fields: effects of simulated atmospherics and 100-Hz magnetic fields on audiogenic seizure in rats (1988)
    Springer
    International journal of biometeorology 32 (1988), S. 17-20 
    Details
    ISSN: 1432-1254
    Keywords: Epilepsy ; Electromagnetic fields ; Rat ; Audiogenic seizure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract In order to study the possible association between epileptic seizures and natural electromagnetic fields, 32 female audiogenic seizure (AGS)-susceptible rats were exposed to simulated 10 kHz and 28 kHz atmospherics and to a sinusoidally oscillating magnetic field with a frequency of 100 Hz and field strength of 1 A/m. After the electromagnetic exposure, seizures were induced in the rats with a sound stimulus. The severity of the seizure was determined on an ordinal scale, the audiogenic response score (ARS). The time from the beginning of the sound stimulus to the onset of the seizure (seizure latency) and the duration of the convulsion was measured. No differences from the control experiments were found in the experiments with simulated atmospherics, but the 100 Hz magnetic field increased the seizure latency by about 13% (P〈0.02). The results do not support the hypothesis that natural atmospheric electromagnetic signals could affect the onset of epileptic seizures, but they suggest that AGS-susceptible rats may be a useful model for studying the biological effects of electromagnetic fields.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01623987
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    Demonstration of correlations between the 8 and 10 kHz atmospherics and the inflammatory reaction of rats after carrageenan injection (1988)
    Springer
    International journal of biometeorology 32 (1988), S. 201-204 
    Details
    ISSN: 1432-1254
    Keywords: Atmospherics ; Carrageenan inflammation ; Rat ; Susceptibility ; Correlations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract Between the mean daily density of 28 kHz atmospherics and the onset of epileptic fits there is a highly significant correlation coefficient (r) of 0.30; there is a negative coefficient of −0.20 between the fits and the mean daily density of 10 kHz atmospherics. The onset of heart infarction is correlated with 28 kHz atmospherics (r=0.15). Furthermore, we have discovered that sudden deafness is also correlated with certain configurations of atmospherics. In this paper we report the following correlation coefficients between the inflammatory reaction of rats to a carrageenan injection (rci) into a hind paw and the mean daily pulse rate of atmospherics of the same day:r=0.49 for the 8 kHz atmospherics (P〈0.02) andr=0.44 for the 10 kHz atmospherics (P〈0.04). The correlations between rci reaction and other atmospherics (12 and 28 kHz) are smaller and not significant. By the method of multiple linear regression we found a multipleR=0.54 between rci reaction and the 8 and 10 kHz atmospherics (the regression function for the rci reaction is 0.15+0.004×8 kHz+0.002×10 kHz,P〈0.05).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01045280
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    The 5-HT1A receptor agonist, 8-OH-DPAT, preferentially activates cell body 5-HT autoreceptors in rat brain in vivo (1988)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 463-471 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00179315
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    Peptide YY (PYY) stimulates intrinsic enteric motor neurones in the rat small intestine (1988)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 287-292 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00173402
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    Age-related scopolamine effects on social and individual behaviour in rats (1988)
    Springer
    Psychopharmacology 95 (1988), S. 344-350 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00181945
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    Substitution and cross-tolerance profiles of anorectic drugs in rats trained to detect the discriminative stimulus properties of cocaine (1988)
    Springer
    Psychopharmacology 95 (1988), S. 364-368 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00181948
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    Changes in behavioural responses to the combined administration of D1 and D2 dopamine agonists in normosensitive and D1 supersensitive rats (1988)
    Springer
    Psychopharmacology 95 (1988), S. 381-385 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00181952
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    The 5-HT1A agonist 8-OH-DPAT increases consumption of palatable wet mash and liquid diets in the rat (1988)
    Springer
    Psychopharmacology 94 (1988), S. 58-63 
    Details
    ISSN: 1432-2072
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00735881
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    Delay-dependent short-term memory deficits in aged rats (1988)
    Springer
    Psychopharmacology 96 (1988), S. 174-180 
    Details
    ISSN: 1432-2072
    Keywords: Aging ; Short-term memory ; Delayed response ; Delayed matching ; Delayed non-matching ; Arecoline ; Physostigmine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Separate groups of rats of three ages (6 month, 15 month or 24 month) were trained in a two-lever operant chamber on one of two versions of a paired-trial delayed response task involving either matching or non-matching of the choice response to a sample lever. The older rats were unimpaired in learning either version of the task during initial training with no (0 s) delay between the sample and choice responses. However, when variable 0–24 s delay intervals were introduced, the 24-month group was impaired on acquisition of the delayed non-matching task, and both the 15- and 24-month groups were impaired on acquisition of the delayed matching task compared to the 6-month group. Deficits in the older groups in asymptotic performance were attributable to an impairment at longer delay intervals whilst maintaining near perfect performance at the shorter delay intervals, suggesting a selective short-term memory impairment. The delay-dependent deficits of the older groups were not ameliorated by the muscarinic agonist arecoline or the cholinesterase inhibitor physostig-mine, and so failed to corroborate a cholinergic interpretation of the observed age-related impairment in short-term memory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177557
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    Effects of diazepam, FG 7142, and RO 15-1788 on schedule-induced polydipsia and the temporal control of behavior (1988)
    Springer
    Psychopharmacology 94 (1988), S. 103-109 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00735889
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    Cholinergic mediation of the discriminative stimulus properties of clozapine (1988)
    Springer
    Psychopharmacology 94 (1988), S. 115-118 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00735891
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    Intra-amygdala injections of corticotropin releasing factor facilitate inhibitory avoidance learning and reduce exploratory behavior in rats (1988)
    Springer
    Psychopharmacology 96 (1988), S. 232-236 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177566
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    Low permeability of the blood-brain barrier to nanomolar concentrations of immunoreactive alpha-melanotropin (1988)
    Springer
    Psychopharmacology 96 (1988), S. 262-266 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177572
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    A role for the mesolimbic dopamine system in the reinforcing properties of diazepam (1988)
    Springer
    Psychopharmacology 94 (1988), S. 133-137 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00735894
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    Hangover hyperthermia in rats: relation to tolerance and external stimuli (1988)
    Springer
    Psychopharmacology 94 (1988), S. 161-166 
    Details
    ISSN: 1432-2072
    Keywords: Hangover ; Thermoregulation ; Tolerance ; Ethanol ; Stress ; Compensatory reactions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The recent finding of rebound hyperthermia in rats on the day after a single IP injection or oral intubation of ethanol was confirmed. In our studies, body temperature measured by rectal probe was significantly decreased for 8 h after 2.5 g/kg ethanol IP and was then significantly elevated 16–24 h after injection; increased vocalization during handling at 24 h was also found. However, rats isolated in a sound-attenuation chamber with remote temperature measurement showed no hyperthermia even though they were hypothermic during intoxication. The results do not support the hypothesis that rebound hyperthermia was caused by either a disruption of circadian rhythms, or by a mild abstinence syndrome alone. Instead, it appears that external stimuli, perhaps related to stress or associated with ethanol administration, are necessary on the day after a moderate dose of ethanol to produce the hyperthermia. Like hangover in humans, hyperthermia was reduced in rats made tolerant to ethanol: both the hypothermia and the rebound hyperthermia were significantly lower on the day after the 12th alternate-day ethanol injection than after the first injection. The aftereffects in rats of acute intoxication are, by definition, hangover signs, and they resemble hangover in humans in several ways, but their relevance as an animal model of hangover remains to be determined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00176838
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    Changes in auditory evoked responses and in the inhibitory action of 5-hydroxytryptophan following chronic treatment with imipramine in the rat (1988)
    Springer
    Psychopharmacology 96 (1988), S. 408-413 
    Details
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptophan ; Imipramine ; Brainstem auditory evoked response ; Middle latency auditory evoked response ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The neurophysiological effects of acute and chronic treatment with the tricyclic antidepressant drug imipramine were investigated. Brainstem (BAER) and middle latency (MLR) auditory evoked responses were monitored in the alert and immobile rat. Daily injection of imipramine (10 mg/kg, IP) for 2 weeks produced a 13% increase in the latency and a 35% reduction in the amplitude of the N17 component of the MLR. Acute imipramine treatment had no effect. There was no observable change in the BAER after either acute or chronic drug administration. Serotonergic function was assessed by studying the inhibitory effects of 5-hydroxytryptophan on the BAER and MLR. Chronic application of imipramine caused an apparent reduction of the effects of 5-hydroxytryptophan (75 mg/kg, IP) on the N17 component of the MLR. This may, however, be due to the shift in baseline latency and amplitude. Inhibition of the BAER by 5-hydroxytryptophan was unaltered by long term exposure to imipramine. Acute treatment with imipramine was without effect on the modulation of the BAER and the MLR by 5-hydroxytryptophan. These results provide evidence that chronic, as opposed to acute, administration of imipramine had an inhibitory effect on auditory processing at the level of the MLR and that this may be associated with a change in the net output of the serotonergic system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00216071
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    Behavioral evidence for the role of noradrenaline in putative anxiolytic and sedative effects of benzodiazepines (1988)
    Springer
    Psychopharmacology 95 (1988), S. 280-286 
    Details
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Triazolopyridazines ; Noradrenaline ; Clonidine ; Yohimbine ; Drug discrimination stimulus ; Fixed ratio performance ; Bicuculline ; Ro 15-1788 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of clonidine on the antianxiety and sedation of benzodiazepines (BZD) were assessed respectively in rats trained in a two-lever diazepam cue discrimination procedure and in single-lever fixed-ratio (FR) water-reinforced performance. Clonidine (10–60 μg/kg) significantly shifted to the left the dose-effect curves of diazepam in the discrimination paradigm. This treatment also shifted generalization dose-effect curves of the diazepam cue to chlordiazepoxide and CL 218872 to the left in the drug discrimination procedure. The diazepam cue was antagonized in a dose-related manner by Ro 15-1788, but not by bicuculline. Clonidine also potentiated the rate-decreasing effects of diazepam on the FR schedule when the dose of diazepam was increased to 0.3 mg/kg, but not the milder rate-decreasing effect of CL 218872 until the dose of CL 218872 was increased to 10 mg/kg. The potentiating effects of clonidine on the stimulus control and depression of diazepam were antagonized by yohimbine. Yohimbine (1.0 mg/kg) also significantly shifted the dose-effect curve of diazepam cue to the right. Bicuculline (3 mg/kg) completely antagonized the rate-decreasing effect of diazepam (1 mg/kg), but significantly potentiated the rate-suppressant effect of clonidine (10 μg/kg). These results suggest that the central noradrenaline (NA) system may be involved not only in the antianxiety, but also the sadative action of BZD. The nature of NA involvement in relation to the different subtypes of BZD receptors requires further exploration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174525
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    The effects of chronic antidepressant treatment in an animal model of anxiety (1988)
    Springer
    Psychopharmacology 95 (1988), S. 298-302 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00181937
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    The α2-adrenoceptor antagonists idazoxan and yohimbine increase rates of DRL responding in rats (1988)
    Springer
    Psychopharmacology 95 (1988), S. 413-417 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00181958
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    Tests of functional equivalence between pimozide pretreatment, extinction and free feeding (1988)
    Springer
    Psychopharmacology 95 (1988), S. 423-426 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00181960
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    Differential effects of the selective D2-antagonist raclopride in the nucleus accumbens of the rat on spontaneous and d-amphetamine-induced activity (1988)
    Springer
    Psychopharmacology 95 (1988), S. 447-451 
    Details
    ISSN: 1432-2072
    Keywords: Nucleus accumbens ; d-Amphetamine activity ; Exploration ; Raclopride ; D2-receptors ; Schizophrenia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of the D2-antagonist raclopride was investigated in two test situations, which are presumed to involve dopamine (DA) transmission within the nucleus accumbens of the rat. Local injection of d-amphetamine sulphate (10 μg/0.5 μl) produced a marked increase in motor activity, measured as motility, locomotion, and rearing, which was dose- and time-dependently antagonised by local injection of raclopride (0.05–5.0 μg/0.5 μl). After an initial decrease, at low doses (0.05–0.25 μg/0.5 μl) an apparent enhancement of the d-amphetamine-induced motor activity appeared, which was most clearly seen with rearing. These lower doses, however, did not induce any clear changes in the exploratory activity in a novel environment (i.e., the second test situation). Only the higher doses used (1.0–5.0 μg/0.5 μl) decreased exploratory activity during the first 5–10 min, also measured as motility, locomotion, and rearing. These data are discussed with respect to the role of D2-receptors within the nucleus accumbens of rats in the motor activity induced by a novel environment and d-amphetamine. Overall, the data underline previous notions that raclopride is a potent antagonist of DA-mediated behaviour.
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    URL: http://dx.doi.org/10.1007/BF00172953
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    The effects of haloperidol on the partial reinforcement extinction effect (PREE): implications for neuroleptic drug action on reinforcement and nonreinforcement (1988)
    Springer
    Psychopharmacology 95 (1988), S. 528-533 
    Details
    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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    URL: http://dx.doi.org/10.1007/BF00172968
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    Pharmacological characterization of the physostigmine stimulus in rats (1988)
    Springer
    Psychopharmacology 95 (1988), S. 553-555 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00172975
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    Infusion of the 5-hydroxytryptamine agonists RU24969 and TFMPP into the paraventricular nucleus of the hypothalamus causes hypophagia (1988)
    Springer
    Psychopharmacology 95 (1988), S. 550-552 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00172974
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    Induction of oral stereotypy following amphetamine microinjection into a discrete subregion of the striatum (1988)
    Springer
    Psychopharmacology 95 (1988), S. 556-559 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00172976
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    Environmental influences on the development of tolerance to the effects of physostigmine on schedule-controlled behavior (1988)
    Springer
    Psychopharmacology 96 (1988), S. 462-467 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02180025
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    DSP4 and Herrnstein's equation: further evidence for a role of noradrenaline in the maintenance of operant behaviour by positive reinforcement (1988)
    Springer
    Psychopharmacology 96 (1988), S. 551-556 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02180039
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    Diazepam blocks the interfering effect of post-training behavioral manipulations on retention of a shuttle avoidance task (1988)
    Springer
    Psychopharmacology 94 (1988), S. 402-404 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00174697
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    Changes in dopamine autoreceptor sensitivity in an animal model of depression (1988)
    Springer
    Psychopharmacology 94 (1988), S. 545-550 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00212853
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    The mode of action of bromocriptine following pretreatment with reserpine and α-methyl-p-tyrosine in rats (1988)
    Springer
    Psychopharmacology 95 (1988), S. 29-33 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00212761
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    Multifocal sites of action involved in dopaminergic-cholinergic neuronal interactions in yawning (1988)
    Springer
    Psychopharmacology 95 (1988), S. 34-37 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00212762
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    Effects of nimodipine on the discriminative stimulus properties ofd-amphetamine in rats (1988)
    Springer
    Psychopharmacology 96 (1988), S. 40-44 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; d-Amphetamine ; Nimodipine ; Diazepam ; Morphine ; Haloperidol ; Calcium channel ; Behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus (DS) properties ofd-amphetamine (AMP) are thought to be mediated by enhanced release of catecholamines, which may involve neuronal calcium influx through voltage sensitive channels. The present study examined the influence of nimodipine, a calcium channel blocker, on the DS properties of AMP. Rats (N=8) were trained to discriminate AMP (0.5 mg/kg, IP) from saline in a two-lever, food-reinforced, drug discrimination paradigm. Nimodipine alone (2.0–5.6 mg/kg, IP) did not substitute for AMP. When given in combination with AMP, 2.0 mg/kg nimodipine increased by less than 2-fold the AMP dose necessary to induce AMP-appropriate responses. Higher doses of nimodipine combined with AMP did not increase the magnitude of this effect. Nimodipine enhanced the effects of AMP on response rate. Haloperidol (0.125 mg/kg) increased by approximately 4-fold, whereas diazepam (0.5 or 1.0 mg/kg) and morphine (5.0 mg/kg) increased by approximately 2-fold the AMP dose necessary to induce AMP-appropriate responses. The interaction with AMP was associated with enhanced reduction of response rate in the tests with diazepam and morphine but not haloperidol. These results suggest that nimodipine attenuates the DS properties of AMP, probably in a non-specific way, due to the ability of nimodipine itself to induce a discriminable internal state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431531
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    Is the discriminative stimulus produced by phencyclidine due to an interaction with N-methyl-d-aspartate receptors? (1988)
    Springer
    Psychopharmacology 96 (1988), S. 87-92 
    Details
    ISSN: 1432-2072
    Keywords: Rat ; Drug discrimination ; NMDA ; Phencyelidine ; ±SKF 10047 ; MK 801 ; CPP ; Ifenprodil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate phencyclidine (PCP) from saline at doses of 2 and 4 mg/kg, using a two-lever food reinforced operant technique. ±N-allylnormetazocine (±SKF 10047), +5-methyl-10,11-dihydro-5H-dibenzo[A,D]cyclohepten-5,10-imine (MK 801), 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) and ifenprodil, which have been shown to antagonise the effects of N-methyl-d-aspartate (NMDA), were tested for their ability to give rise to PCP-appropriate responding. In rats trained at both doses of PCP, ±SKF 10047 (2–12 mg/kg) and MK 801 (0.0125–0.2 mg/kg) produced dose-related responding on the lever associated with PCP injection. The relative potency of these two compounds was the same in the two groups of animals, but their absolute potencies to produce a PCP-like discriminative stimulus were dependent on the training dose of PCP. In contrast, neither the competitive NMDA antagonist CPP (4–20 mg/kg) nor the non-competitive antagonist ifenprodil (2–12 mg/kg) produced PCP-appropriate responding and ifenprodil (4-mg/kg) neither potentiated nor antagonised PCP. These findings are discussed in the light of the hypothesis that the behavioural effects of PCP are mediated via a reduction of neurotransmission at the NMDA-subtype of glutamate receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431538
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    Tolerance and selective cross-tolerance to the motivational effects of opioids (1988)
    Springer
    Psychopharmacology 96 (1988), S. 110-115 
    Details
    ISSN: 1432-2072
    Keywords: Tolerance ; Opioids ; Reinforcement ; Place conditioning ; Morphine ; U-69593 ; d-Amphetamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The issue of whether tolerance develops to the motivational effects of opioids was addressed by use of an unbiased place preference conditioning procedure. Administration of the μ-opioid agonists morphine or fentanyl produced dose-related preferences for the drug-associated place in control rats. In contrast, the κ-opioid agonist, U-69593 produced conditioned place aversions. Non-contingent administration of morphine (5.0 mg/kg/12 h) for 4 days prior to conditioning resulted in tolerance to its reinforcing effects, and cross-tolerance to the effects of fentanyl. No cross-tolerance to the motivational effects of the psychostimulantd-amphetamine or the κ-opioid agonist U-69593 was observed. Chronic administration of U-69593 prior to conditioning produced tolerance to its aversive effects. This treatment did not, however, modify the reinforcement produced by morphine. These data demonstrate that tolerance develops to both the reinforcing and aversive properties of opioids and suggest that differential cross-tolerance may provide a useful method for determining the pharmacological basis underlying drug-induced motivational effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431542
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    Potential interactions between GABAb and cholinergic systems: baclofen augments scopolamine-induced performance deficits in the eight-arm radial maze (1988)
    Springer
    Psychopharmacology 96 (1988), S. 116-120 
    Details
    ISSN: 1432-2072
    Keywords: Radial maze performance ; Motor activity ; Pharmacological interactions ; Baclofen ; Scopolamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sixteen male Fischer-344N rats were trained on a eight-arm radial maze task for food reinforcement. The effects of various doses of baclofen (1.25 or 2.50 mg/kg) and scopolamine (0.188, 0.375, and 0.750 mg/kg) were determined alone and in combination. Relative to vehicle controls, baclofen alone did not affect performance in the radial arm maze (number correct in the first eight responses, total errors) or the time required to complete the maze. Scopolamine alone decreased the number of correct responses in the first eight arm choices, while increasing both the number of errors and the time necessary to complete the maze. When the two drugs were co-administered, baclofen had no effect on the number of errors or time required to complete the maze in the presence of scopolamine; however, in combination with the high dose of scopolamine, it significantly inreased the number of errors made during the first eight choices. Baclofen thus can exacerbate some radial arm maze dificits produced by an anticholinergic drug. In a subsequent experiment to test the interaction between scopolamine and baclofen using a nonlearned behavior, baclofen (1.25 and 2.5 mg/kg) did not affect motor activity, whereas all doses of scopolamine (0.188–0.75 mg/kg) increased activity. The higher dose of baclofen attenuated scopolamine-induced hypermotility by 50%, but the lower dose of baclofen was not effective. These data demonstrate pharmacological interactions between baclofen, a drug used clinically for spaticity, and a drug having anticholinergic properties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431543
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    Facilitation of brain stimulation reward byΔ 9-tetrahydrocannabinol (1988)
    Springer
    Psychopharmacology 96 (1988), S. 142-144 
    Details
    ISSN: 1432-2072
    Keywords: Marijuana ; Cannabis ; Cannabinoids ; Δ 9-tetrahydrocannabinol ; THC ; Brain stimulation reward ; Intracranial self-stimulation ; ICSS ; Reinforcement ; Medial forebrain bundle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present experiment explored whetherΔ 9-tetrahydrocannabinol (Δ 9-THC), the psychoactive ingredient in marijuana, shares with other drugs of abuse the ability to facilitate brain stimulation reward acutely, as measured by clectrical intracranial self-stimulation (ICSS). Laboratory rats were implanted with stimulation electrodes in the medial forebrain bundle, and trained to stable performance on a self-titrating threshold ICSS paradigm.Δ 9-THC, at a dose believed pharmacologically relevant to moderate human use of marijuana, acutely lowered ICSS thresholds, suggesting that marijuana acts on similar CNS hedonic systems to most other drugs of abuse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431546
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    Apomorphine anorexia: the role of dopamine receptors in the ventral forebrain (1988)
    Springer
    Psychopharmacology 96 (1988), S. 135-141 
    Details
    ISSN: 1432-2072
    Keywords: Apomorphine ; Sulpiride ; SCH-23390 ; Central drug administration ; Dopamine autoreceptors ; Feeding behaviour ; Microstructural analysis ; Eating rate ; Eating time ; Open field ; Nucleus accumbens ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The inhibition of feeding following the administration of apomorphine, systemically or directly into the nucleus accumbens/ventral striatum, was studied using a microstructural analysis paradigm. On systemic administration, apomorphine reduced food consumption, eating rate and eating time; the effects were blocked by sulpiride but not by SCH-23390. Two doses of apomorphine were administered centrally. Both doses reduced total food intake and eating rate; only the higher dose also reduced eating time; all of these effects were blocked by sulpiride pretreatment. Only the lower dose reduced locomotor activity and rearing in the open field. The results suggest that apomorphine reduces eating rate by an action on dopamine (DA) axon terminal autoreceptors. We have previously demonstrated that apomorphine reduces eating time by an action on DA cell body autoreceptors. Therefore, the two populations of DA autoreceptors appear to be differentially involved in behaviour.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431545
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    Interaction between ethanol and caffeine in operant behavior of rats (1988)
    Springer
    Psychopharmacology 96 (1988), S. 194-205 
    Details
    ISSN: 1432-2072
    Keywords: Caffeine ; Ethanol ; Interaction ; Rat ; Operant behavior ; Spatial alternation ; Microanalysis of behavior ; Blood levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interaction between ethanol and caffeine on operant behavior was studied in 24 water-deprived male rats trained in a discrete trial spatial alternation schedule with water as reinforcer. One single drug dose-response experiment or one dose combination of ethanol and caffeine (including the associated control treatments) was run on 4 successive days in 1 week. The four treatments of 1 week were administered to each animal in a distinct order according to the 24 possible permutations. In the single drug weeks, ethanol (0.25, 0.5, 0.75 and 1.0 g/kg IP) or caffeine (5, 10, 20, and 40 mg/kg PO) were administered 15 min before the session. In four interaction experiments all combinations of two doses of ethanol (0.5 and 1.0 g/kg IP) and two doses of caffeine (25 and 50 mg/kg PO) were employed. Ethanol and caffeine alone showed both dose-dependently decreased choice accuracy and increased response latency and passiveness. In combination, caffeine normalized the ethanol-induced alterations in ITI response rate and pause length but potentiated the effects on choice accuracy, latency and number of pauses. The results are interpreted in terms of effects of these drugs on attentional and arousal processes, and the test procedure is proposed as a screening tool for the preclinical assessment of ethanol-drug interactions.
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    URL: http://dx.doi.org/10.1007/BF00177560
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    Increased food intake in satiated rats induced by the 5-HT antagonists methysergide, metergoline and ritanserin (1988)
    Springer
    Psychopharmacology 96 (1988), S. 237-242 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00177567
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    The effect of chronic adriamycin treatment on heart kidney and liver tissue of male and female rat (1988)
    Springer
    Archives of toxicology 61 (1988), S. 275-281 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00364850
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  • 88
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    Electronic Resource
    Organ-specific effects of naphthalene on tissue peroxidation, glutathione peroxidases and superoxide dismutase in the rat (1988)
    Springer
    Archives of toxicology 61 (1988), S. 480-483 
    Details
    ISSN: 1432-0738
    Keywords: Rat ; Naphthalene ; Peroxidation ; Glutathi one peroxidase ; Superoxide dismutase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male, weanling Blue-Spruce rats were treated with naphthalene (p.o.) in defined dose increments up to 750 mg/kg body weight over 9 weeks. At necropsy, treated rats showed a 20% decrease in body weight compared to controls. Naphthalene treatment resulted in enhanced peroxidation (p〈0.001) only in the liver. This increased peroxidation was associated with reductions (p〈0.05) in the activity of the selenoenzyme glutathione peroxidase in hepatic cytosolic fractions and an associated increase (p〈0.05) in the selenium-independent glutathione peroxidase. No increase in peroxidation was observed in the lung, eye or heart of these rats and the activities of the selenoenzyme and the selenium-independent glutathione peroxidases were also unaffected by naphthalene in these organs. Naphthalene also did not affect superoxide dismutase activity in any of the organs examined. Thus, in addition to the known effects of naphthalene on tissue glutathione, naphthalene-induced reductions in the selenoenzyme glutathione peroxidase can also contribute to peroxidation in the liver and must be considered as a contributing factor in naphthalene toxicity in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00293694
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  • 89
    Electronic Resource
    Electronic Resource
    Nephrotoxicity of butylated hydroxytoluene in phenobarbital-pretreated male rats (1988)
    Springer
    Archives of toxicology 61 (1988), S. 359-365 
    Details
    ISSN: 1432-0738
    Keywords: Butylated hydroxytoluene ; Nephrotoxicity ; Phenobarbital ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A single large dose of butylated hydroxytoluene (BHT, 1000 mg/kg) in male Fischer 344 rats produced some renal damage, reduced accumulation of p-aminohippuric acid in renal slices, proteinuria and enzymuria, in addition to hepatic damage. Further, prior administration of phenobarbital (80 mg/kg, i. p., daily for 4 days) in the high-dose BHT-treated male rats produced renal damage accompanied by slight tubular necrosis. The renal damage was confirmed by biochemical and histological changes. These changes were dose dependent, with a maximum at 24 h after BHT administration, but had returned to the normal range by 48 h. Female rats, on the other hand, were less susceptible to BHT-induced renal and hepatic damage than male rats. The results indicate sex differences in BHT-induced renal or hepatic damage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00334616
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  • 90
    Electronic Resource
    Electronic Resource
    Effect of buthionine sulfoximine on orthophenylphenol-induced hepato- and nephrotoxic potential in male rats (1988)
    Springer
    Archives of toxicology 62 (1988), S. 452-457 
    Details
    ISSN: 1432-0738
    Keywords: Orthophenylphenol ; Metabolites ; Buthionine sulfoximine ; Hepatotoxicity ; Nephrotoxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A single oral administration of orthophenylphenol (OPP, 1400 mg/kg; about half the LD50) to male Fischer 344 rats produced an elevation of serum transaminase activity 24 h later. Pretreatment with l-buthionine-S,R-sulfoximine (BSO, 900 mg/kg) in the OPP-treated rats potentiated the hepatic and renal damage which was accompanied by necrosis. Six hours after the administration of OPP (700 or 1400 mg/kg), hepatic and renal glutathione (GSH) levels decreased with increasing dosage. Hepatic GSH depletion with OPP was enhanced with BSO pretreatment and the recovery of GSH in both organs was slow in the high-dose OPP group. These results suggest that hepatic and renal damage is associated with a serious and prolonged GSH depletion. When either phenyl-p-benzoquinone (PBQ) or phenylhydroquinone (PHQ), which are intermediates of OPP, was administered orally to rats at 700 or 1400 mg/kg, the mortality with the high dose of PBQ was 75% at 24 h. The serum transaminase activity and UN level increased with the low dose of PBQ, accompanied by necrotic hepatocytes. The toxic effects of PHQ on kidney or liver were less than those on PBQ. These observations suggest that the liver and kidney may be target organs for toxic actions of a large dose of OPP and its intermediate, PBQ.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00288349
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  • 91
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    Electronic Resource
    Gentamicin plasma concentrations in pregnant and non-pregnant rats and fetuses after single and multiple injections (1988)
    Springer
    Archives of toxicology 62 (1988), S. 232-235 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00570148
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  • 92
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    Electronic Resource
    Influence of di-butyltin dilaurate on brain neurotransmitter systems and behavior in rats (1988)
    Springer
    Archives of toxicology 61 (1988), S. 373-377 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00334618
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  • 93
    Electronic Resource
    Electronic Resource
    Prenatal toxicity of acyclovir in rats (1988)
    Springer
    Archives of toxicology 61 (1988), S. 468-479 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00293693
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  • 94
    Electronic Resource
    Electronic Resource
    Effects of Fusarenon-X and T-2 toxin on intestinal absorption of monosaccharide in rats (1988)
    Springer
    Archives of toxicology 61 (1988), S. 489-495 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00293696
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  • 95
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    Electronic Resource
    Urinalysis for detection of chemically induced renal damage (3) — establishment and application of radioimmunoassay for lysozyme of rat urine (1988)
    Springer
    Archives of toxicology 62 (1988), S. 60-65 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316259
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  • 96
    Electronic Resource
    Electronic Resource
    In vivo and in vitro effects of methylmercury on the activities of aminoacyl-tRNA synthetases in rat brain (1988)
    Springer
    Archives of toxicology 62 (1988), S. 470-472 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00288352
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  • 97
    Electronic Resource
    Electronic Resource
    Renal toxicity of the antitumor drug N2-methyl-9-hydroxyellipticinium acetate in the wistar rat (1988)
    Springer
    Archives of toxicology 61 (1988), S. 292-297 
    Details
    ISSN: 1432-0738
    Keywords: Nephrotoxicity ; Cytostatic drug ; Celiptium ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Celiptium (N2-methyl-9-hydroxy-ellipticinium) is an antitumoral agent used to treat bone metastases from breast carcinomas. This new drug appeared to be of great interest because of the absence of hepato-or myelotoxicity. Three different investigators recently mentioned cases of celiptium-induced renal failure. We therefore undertook a study of renal function and morphology in female Wistar rats. Two single i.v. doses (10 or 20 mg/kg) were administered and animals were sacrificed 4, 8, 15, 28 and 60 days after injection. One group of rats received multiple doses, 5 mg/kg/week for 8 weeks. No mortality was observed. With the 10 mg/kg single dose creatinine clearance (Ccr) and urinary enzymes did not change, and tubular lesions were rare. With the 20 mg/kg single dose CCr decreased on day 4 and returned to normal on day 28. Urinary enzyme excretion (AAP, NAG, γGT) increased. Renal lesions were diffuse with tubular necrosis, luminal dilation and later (day 28) interstitial cellular infiltration. These lesions persisted on day 60 and appeared to be irreversible. Ultrastructural studies showed numerous large fat droplets in proximal tubular cells. Glycerol concentrations in renal cortex homogenates were increased while phospholipids are slightly decreased. With 5 mg/kg every week (multiple doses) Ccr decreased and tubular lesions similar to the observed with the 20 mg/kg single dose were seen. Thus celiptium induced dose-dependent nephrotoxicity in rats with prolonged tubular alterations. Since it has been shown that renal tubular cells metabolized celiptium in vitro into electrophilic intermediates, we suggest that free radicals and quinone derivatives may contribute to peroxidation of unsaturated fatty acids and play a role in the nephrotoxicity of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00364852
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  • 98
    Electronic Resource
    Electronic Resource
    Distribution and elimination of (14C)-2-ethylhexyl acrylate radioactivity in rats (1988)
    Springer
    Archives of toxicology 62 (1988), S. 346-350 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00293621
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  • 99
    Electronic Resource
    Electronic Resource
    Gross-structural defects in rats after acyclovir application on day 10 of gestation (1988)
    Springer
    Archives of toxicology 62 (1988), S. 8-14 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316250
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  • 100
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    Electronic Resource
    Electron microscopic results on the ventral prostate of the rat after CdCl2 administration. A contribution towards etiology of the cancer of the prostate (1988)
    Springer
    Journal of cancer research and clinical oncology 114 (1988), S. 273-278 
    Details
    ISSN: 1432-1335
    Keywords: Prostate ; Rat ; Electron microscope
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prostate epithelium of rats which received repeated cadmium chloride (CdCl2) injections showed a gradual disruption of structural differentiation. Electron microscopy studies revealed severe changes in the ultrastructure affecting all epithelial cell organelles, particularly the nuclei, rough endoplasmatic reticulum, the golgi apparatus, and mitochondria. The cells infiltrating the stroma contained secretory vacuoles and their nuclear evaginations on the invasion front showed similarities to ultrastructural pathological changes in man. Examination of the ventral prostate following oral CdCl2 administration revealed changes ranging in severity up to dysplasia, but there was no evidence of carcinoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00405833
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