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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 179 (1989), S. 221-226 
    ISSN: 1432-0568
    Keywords: GABA ; Immunocytochemistry ; Gastrointestinal tract ; Epithelium ; Enteroendocrine cells ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Frozen sections of the corpus ventriculi, antrum pyloricum, duodenum, jejunum, ileum and colon from animals perfusion fixed with glutaraldehyde were treated with an antiserum specific for glutaraldehyde-fixed GABA and processed by the peroxidase antiperoxidase method. Semithin plastic sections from the antrum pyloricum were treated similarly. Stained cells appeared in the epithelium of all segments examined except the corpus ventriculi. The highest density of cells was observed along the major curvature of the antrum pyloricum. Here they were located in the bottom half of the gastric glands. Many of the cells showed a process extending towards the glandular lumen. No significant staining in the epithelium appeared when the antiserum was preincubated with glutaraldehyde-GABA complexes, nor when the anti-GABA serum was exchanged with anti-glycine or preimmune serum. The present findings and previous physiological data suggest that GABA may play a role in gut endocrine regulation.
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  • 2
    ISSN: 1432-0568
    Keywords: Pyramidal tract ; Rat ; Development ; Axon loss ; Myelination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A quantitative electron microscopic analysis was undertaken of the development of the pyramidal tract, at the level of the third cervical spinal segment, in rats ranging in age from the day of birth to three months old. The axon number was calculated as the product of axon density, determined in a systematic random sample of electron micrographs, and tract area. During the first postnatal week the tract contains thin unmyelinated axons and growth cones. Growth cones are abundant in neonatal rats, but can still be observed occasionally at the end of the first postnatal week, indicating a continuous addition of pyramidal tract axons during the first postnatal week. Myelination starts around P10. By the end of the first postnatal month approximately 50% of the axons have already been myelinated. Myelination proceeds during further maturation, but in the three month old rat 28% of the axons are still unmyelinated. The total number of axons increases rapidly after birth up to 153 000 at the fourth postnatal day. Subsequently, the number of axons is reduced by nearly 50% to 79 000 in the adult rat. The axon loss is most prominent during the second postnatal week, when 32 000 axons are climinated, but continues for several weeks at a slower rate.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 180 (1989), S. 207-212 
    ISSN: 1432-0568
    Keywords: Thyrotroph (TSH cell) ; Anterior pituitary ; Immunogold electron microscopy ; Postnatal development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thyrotrophs (TSH cells) of the rat anterior pituitary identified by immunogold electron microscopy were classified into three subtypes according to their morphological characteristics: Immature type TSH cells are oval with a few small secretory granules (50–100 nm in diameter) and poorly developed cell organelles. These cells are frequently found in the neonatal stage between birth and 10 days of age. The intermediate type is polygonal or stellate, containing a moderate number of medium sized secretory granules (80–120 nm in diameter) and moderately or well developed cell organelles. Cells of this type are often found between 10 and 30 days of age. Mature type cells are large and polygonal in shape, and contain many large secretory granules (120–180 nm in diameter) and well developed cell organelles. Cells of the last type are frequently found at more than 30 days of age. At 45 days of age the mature type TSH cells make up about 70% of all TSH cells. The proportion of immature type cells was shown to decrease while the proportion of the mature type TSH cells increases, as the animal grows.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 180 (1989), S. 243-257 
    ISSN: 1432-0568
    Keywords: Dorsal lateral geniculate nucleus ; Synapse formation ; Synaptic glomerulus ; Rat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Synapse formation and maturation were examined in the rat dorsal lateral geniculate nucleus (dLGN) from birth to adulthood. Examination of animals, whose ages were closely spaced in time, showed that the maturation of the synaptic organization of the nucleus takes place chiefly during the first 3 weeks of postnatal life. This period of maturation may be divided into 3 broad stages. During the first stage, which spans the first 4 days of life, there are only a few immature synapses scattered throughout the nucleus; occasionally aggregates of 3 or 4 synapses are encountered. Dendrodendritic synapses first appear at the end of this stage. The second stage, which lasts from the end of the first stage through day 8, is characterized by intensive synaptogenesis as well as extensive growth and degeneration. For the first time, large boutons resembling retinal terminals form multiple synaptic contacts with dendrites and dendritic protrusions; these synaptic arrangements are partially covered by glial processes. A feature characteristic of the developing dLGN during the first 2 postnatal weeks, and particularly during the second stage, is the presence of membrane specializations that resemble vacant postsynaptic densities. These specializations, which may be unapposed or opposite another neuronal process, decrease in frequency as the number of synapses increases. It is not known whether these densities are converted to synapses or whether they result from loss of presynaptic elements. The third stage in the process of synaptogenesis, which spans a period between days 10 and 20, is characterized by myelination and by the diminution of growth cones, degenerating profiles and vacant postsynaptic densities. There is also a very significant increase in the number and maturation of synapses including synaptic glomeruli. However, it is not until the end of this stage that synapses appear qualitatively indistinguishable from synaptic arrangements identified in adult animals.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 179 (1989), S. 449-456 
    ISSN: 1432-0568
    Keywords: Corticospinal tract ; Development ; Myelination ; Pyramidal tract ; Anterograde tracing ; Electronmicroscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Horseradish-peroxidase was used to anterogradely label and thus to trace the growth of corticospinal axons in rats ranging in age from one day to six months. Three to eight HRP-gels were implanted in the left cerebral hemisphere of the cortex. In each spinal cord three levels were studied, the cervical intumescence (C5), the mid-thoracic region (T5) and the lumbar enlargement (L3). The methodology employed for the electron microscopic visualization of HRP has been described previously (Joosten et al. 1987a). The outgrowth of labelled unmyelinated corticospinal tract axons in the rat spinal cord primarily occurs during the first ten postnatal days. The outgrowth of the main weve of these fibres is preceded by a number of pathfinding axons, characterized by dilatations at their distal ends, the growth cones. By contrast, later appearing unmyelinated axons, which presumably grow along the pathfinding axons, do not exhibit such growth cones. The first labelled pioneer axons can be observed in the cervical intumescence at postnatal day one (P1), in the mid-thoracic region at day three (P3) and in the lumbar enlargement at day five (P5). Prior to the entrance of the axons, the prospective corticospinal area or the pre-arrival zone is composed of fascicles consisting of unlabelled, unmyelinated fibres surrounded by lucent amorphous structures. During the outgrowth phase of the corticospinal fibres some myelinated axons could be observed within the outgrowth area even before day 14. These axons, however, were never labelled. These findings strongly suggest that the outgrowth area, which is generally denoted as the pyramidal tract, contains other axons besides the corticospinal fibres (and glial cells). The process of myelination of the labelled corticospinal tract axons in the rat spinal cord starts rostrally (C5) at about day 14 and progresses caudally during the third and fourth postnatal weeks. Although myelination seems to be largely complete at day 28 at all three spinal cord levels, some labelled unmyelinated axons are still present in the adult stage.
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  • 6
    ISSN: 1432-0568
    Keywords: Melatonin synthesis ; Pineal gland ; Rat ; “Synaptic” ribbons ; Sympathetic stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Melatonin metabolism in the mammalian pineal gland is under the clear influence of sympathetic fibers originating in the superior cervical ganglia (SCG). Previous studies suggested that pineal “synaptic” ribbons (SR) as well are regulated by the gland's sympathetic innervation. To gain more insight into the mechanisms involved, we examined the effects of sympathetic stimulation on SR number and on the activity of melatonin forming enzymes, serotonin N-acetyltransferase (NAT) and hydoxyindole-O-methyltransferase (HIOMT). The SCG in adult male rats were stimulated electrically during daytime for either 15 or 120 min. Immediately following stimulation, the glands were removed and processed for electron microscopy and for the determination of NAT and HIOMT activities. No differences in pineal SR number, size or location were found in rats stimulated with either parameters when compared with sham-stimulated or control animals. While the activity of HIOMT remained unchanged, the activity of NAT was also unaltered following 15 min of stimulation, but was augmented approximately three-fold in animals stimulated for 120 min. It is concluded that if SR in the rat pineal gland are under sympathetic control, the regulation is different from that involved in melatonin formation.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 79 (1989), S. 149-153 
    ISSN: 1432-0533
    Keywords: Lead ; Rat ; Cerebellum ; Particle-induced X-ray emission (micro-PIXE)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of lead in the cerebellum of suckling Sprague-Dawley rats was examined using a nuclear microprobe for elemental mapping of tissue sections (particle-induced X-ray emission, 3-μm beam of 2.5 MeV protons; micro-PIXE). The rats were injected intraperitoneally with a lead-containing vehicle or vehicle only from ages 1 to 14 days. The calculated doses were 7.8 (low-dose) and 15.6 (high-dose) μg lead/g body weight. The rats were killed at 20 days of age. The vascular system was rinsed quickly with 0.15 M ammonium acetate to obtain determinations of intra-parenchymal lead with minimal influence of lead bound to erythrocytes and plasma proteins. Brains were frozen in propane/propylene in liquid nitrogen. Cryostat sections, 15 μm thick, were air dried on formvar coats that covered a hole, 15 mm in diameter, in a plastic disc, and were used for lead analysis by micro-PIXE. Very low concentrations of lead were found in the brain of controls. Lead levels in homogenates from cerebrum and cerebellum measured by atomic absorption spectrometry (AAS) were: low-dose 1.2–2.2 μg/g wet weight and high-dose 1.4–2.4 μg/g wet weight. The lead levels measured with the micro-PIXE method were in good agreement with the levels found with AAS. Lead was present in the cerebellar white matter in two to three times higher amounts than in the cortical grey (low-dose white matter 11–18 μg/g dry weight, grey matter 2.0–5.5 μg/g dry weight). This was true for both low and high dose exposed rats. Lead concentrations in rats subjected the high-dose lead exposure were approximately 60% higher than those in low-dose exposed rats. Concentrations were lower in the Purkinje cell layer than in other parts of the cortex. These new findings on the distribution of lead in suckling rats are discussed in relation to the pathogenesis of experimental lead encephalopathy.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 78 (1989), S. 264-269 
    ISSN: 1432-0533
    Keywords: Skeletal muscle ; Regeneration ; Growth factors ; Growth hormone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Against the background of the importance of growth hormone (GH) for normal muscle growth, a study was performed to investigate whether lack of GH after hypophysectomy affects the cell proliferation and the local production of insulin-like growth factor-I (IGF-I) in the early stages of muscle regeneration in adult rats. The level of IGF-I in the serum of hypophysectomised rats was reduced to about 30% of that of controls. The incorporation of [methyl-3H]thymidine into the regenerating muscle showed a peak 6 days after the operation and then gradually declined to the end of the period of study 30 days after initiation of regeneration by ischemic necrosis. The DNA content rose to a maximum level after 6–8 days, and remained high after 30 days. There was no major difference in the incorporation of [3H]thymidine in regenerating muscle of hypophysectomised and control rats, but the DNA concentration in the regenerating muscles of hypophysectomised rats was significantly reduced after 30 days. There was a corresponding reduction in the number of nuclei per muscle fibre, indicating that hypophysectomy has a small effect on the cell proliferation during the early stages of muscle regeneration. Immunohistochemical demonstration of IGF-I in the regenerating muscle revealed the transient presence of immunoreactive material in satellite cells and myotubes after 6 to 8 days of regeneration but no immunoreactivity after 30 days. No obvious difference was observed between hypophysectomised and control rats, indicating that the endogenous production of IGF-I in regenerating skeletal muscle can occur independently of GH.
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  • 9
    ISSN: 1432-0533
    Keywords: Somatostatin ; Immunohistochemistry ; Aganglionosis ; Man ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of somatostatin-like immunoreactive (SOM-LI) nerves was elucidated immunohistochemically in the gut tissues from patients with Hirschsprung's disease and congenital aganglionosis rats. In the normoganglionic human colon, SOM-LI nerve cell bodies were found to a greater extent in the submucous plexus and to a lesser extent in the myenteric plexus. However, they were rarely observed in both the plexuses of the oligoganglionic segment. SOM-LI nerve fibres were widely distributed in the aganglionic bowel. The circular muscle layer of the distal aganglionic segment was densely innervated by SOM-LI nerve fibres which are probably derived from the extrinsic, hypertrophic nerve bundles. A decreased number of the intramuscular nerves fibres were seen in the proximal aganglionic segment. In the colon and rectum from adult and 21-day-old rats, SOM-LI cell bodies were numerous in both plexuses. On the other hand, enteric neurons were completely lacking from the colon and rectum of congenital aganglionosis rats of 21 days old. No neuronal elements staining for SOM were disclosed in these aganglionic segments of mutant rats. A possible origin and pathophysiological role of the extrinsic nerve fibres containing SOM in the diseased bowel are discussed. It is concluded that SOM-LI nerves in the human distal colon comprise both intrinsic and extrinsic elements, while SOM nerves in the rat colon and rectum are of only intrinsic origin.
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  • 10
    ISSN: 1432-1432
    Keywords: Carcinoembryonic antigen ; Evolution ; Gene family ; Human ; Rat ; Synonymous substitutions ; Silent molecular clock ; Evolutionary trees
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Various rodent and primate DNAs exhibit a stronger intra- than interspecies cross-hybridization with probes derived from the N-terminal domain exons of human and rat carcinoembryonic antigen (CEA)-like genes. Southern analyses also reveal that the human and rat CEA gene families are of similar complexity. We counted at least 10 different genes per human haploid genome. In the rat, approximately seven to nine different N-terminal domain exons that presumably represent different genes appear to be present. We were able to assign the corresponding genomic restriction endonuclease fragments to already isolated CEA gene family members of both human and rat. Highly similar subgroups, as found within the human CEA gene family, seem to be absent from the rat genome. Hybridization with an intron probe from the human nonspecific cross-reacting antigen (NCA) gene and analysis of DNA sequence data indicate the conservation of noncoding regions among CEA-like genes within primates, implicating that whole gene units may have been duplicated. With the help of a computer program and by calculating the rate of synonymous substitutions, evolutionary trees have been derived. From this, we propose that an independent parallel evolution, leading to different CEA gene families, must have taken place in, at least, the primate and rodent orders.
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  • 11
    ISSN: 1432-0738
    Keywords: Cadmium ; Zinc ; Neonate ; Thymus ; Birth weight ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cadmium exposure during pregnancy (by means of daily subcutaneous injections of 4.4 μmol/kg to the mother) on the neonates were investigated. No effect was observed on fetal or neonatal body weights, nor on neonatal liver weights. These parameters were examined up to 5 weeks after birth. The weight of neonatal thymuses was decreased 7 and 14 days after birth due to cadmium exposure of the mothers as compared with controls. This may be caused by zinc deficiency, because zinc concentrations in fetal and neonatal livers after cadmium exposure were found to be very low 20 days after conception and 5 h after birth. Cadmium concentration in neonatal liver decreased; however, cadmium in malignant liver increased as age increased. In the mother, cadmium was transferred to the milk, as it was demonstrated in the stomach contents of the pups. Simultaneous administration of zinc in amounts equimolar to cadmium did not have any noticeable effect on the amount of cadmium transferred to the fetus or on cadmium concentrations in any of the organs investigated. It could not prevent zinc deficiency in fetal and neonatal liver. In addition, growth retardation of the thymus from exposed pups could not be prevented by zinc administration.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 63 (1989), S. 320-324 
    ISSN: 1432-0738
    Keywords: Cadmium ; Rat ; Mechanical strength of bones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanical properties of the bones of young, adult and old rats administered various concentrations of cadmium were measured to prove the direct effect of cadmium on the bones of young rats. The young rats were divided into three subgroups, which were administered 0 (control), 5 and 10 ppm cadmium, respectively. The adult rats were subdivided into six groups, administered 0, 10, 20, 40, 80 and 160 ppm cadmium, respectively. The old rats were divided into three subgroups, which were administered 0, 80, and 160 ppm cadmium, respectively. The length of the administration was 4 weeks in every group. The decrease in the mechanical strengths of bones of young rats administered with cadmium was observed. On the other hand, no change in mechanical strength of bones was observed in the case of adult and old rats, administered up to 160 ppm cadmium. The correlation between the cadmium in bones and the decrease in the strength of the bone shows that cadmium directly affects the mechanical properties of bones of young rats.
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  • 13
    ISSN: 1432-0738
    Keywords: Tellurium ; Rat ; Toxicology ; Immunomodulator ; Drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male and female Sprague Dawley rats were injected intraperitoneally for 4 weeks with ammonium trichloro (dioxyethylene-0-0′-) tellurate, an immunomodulating drug at closes ranging from 3 to 24 mg/kg/week. Routine laboratory examinations included body weight, food consumption, clinical chemistry and hematological examinations. At termination of the experiment, all rats were sacrificed and subjected to a detailed necropsy. Few mortalities were recorded during the course of the study. Clinical signs included hind limb paresis and paraphimosis. A garlic odor pervaded the room. Body weight and food consumption were adversely affected in a dose-related manner. Effects were elicited on the hematological system; changes being noted in the platelet and leukocyte counts as well. Clinical chemistry evaluation revealed signs of hepatoxicity, especially in the female treated groups. The level of beta-globulin was increased. At necropsy organs were found to have a grayish-blue discoloration. Tellurium related histopathological changes were observed in the eyes, liver, thymus, bone marrow, heart and kidneys. An attempt has been made to compare the toxicity of this drug with other tellurium-containing compounds. A good correlation was found. Novel effects of the drug were retinopathy and replacement of bone marrow by bony or fibrous tissue. The possibility that some of the effects may have been elicited due to selenium-vitamin E deficiency has been considered.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 63 (1989), S. 43-46 
    ISSN: 1432-0738
    Keywords: Styrene ; Testes ; Rat ; Enzymes ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Styrene was administered through gavage to adult male rats for 60 days. At the lower dose of 200 mg/ kg/day no overt signs of testicular toxicity were observed, while at the higher dose of 400 mg/kg/day activities of some marker enzymes for testicular function were found to be altered significantly, along with a decrease in spermatozoa number. Histopathological studies revealed marked degeneration of seminiferous tubules and lumen devoid of sperms, further confirming testicular toxicity of styrene. The present study suggests an overall sensitivity of the male reproductive system towards styrene exposure.
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  • 15
    ISSN: 1432-0738
    Keywords: Methylmercury ; Protein synthesis ; Dorsal root ganglion ; Two-dimensional electrophoresis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dorsal root ganglia from control and methylmercury(MeHg)-treated rats were incubated in vitro with 35S-methionine ant the proteins synthesized were analyzed by two-dimensional electrophoresis. The double labelling method, in which proteins of control dorsal root ganglia labelled in vitro with 3H-leucine were added to each of the two samples as an internal standard, was used to minimize unavoidable errors arising from the resolving procedure itself. The results obtained showed that the effect of MeHg on the synthesis of proteins in dorsal root ganglia was not uniform for individual protein species in the latent period of MeHg intoxication. Among 200 protein species investigated, 157 showed inhibition of synthesis close to that of the total proteins in the tissue (68% of the control). Among the remaining protein species, 20 showed real stimulation of synthesis, whereas 7 were moderately inhibited and 16 were inhibited more strongly than the total proteins in the tissue. These results suggest that the effect of MeHg on the synthetic rates for protein species in dorsal root ganglia differs with the species, and that unusual elevation or reduction of the synthesis of some protein species caused by MeHg may lead to impairment of normal nerve functions.
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  • 16
    ISSN: 1432-2307
    Keywords: Hyperoxia ; Lung broncho-vascular reaction ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to clarify the early phenomena involved in the lung reaction to hyperoxia, twenty adult male rats were exposed to 100% oxygen at 1 ATA. Morphological pulmonary lesions were detectable after only 24 h hyperoxia, and included vasoconstriction and perivascular oedema, bronchiolar constriction, and pericyte reaction. The lesions were irregularly scattered within the lung parenchyma and occurred preferentially in areas centred on bronchiolo-vascular stems. Even at the latest stages, pulmonary heterogeneity was obvious, from the coexistence of areas damaged at different times. Neuro-epithelial-bodies were found under the bronchiolar epithelium; the morphological aspect of the neuro-endocrine cells observed was consistent with hyperoxia-induced modulation of their secretory activity. Taken together, our findings show the speed of development of hyperoxia-induced pulmonary changes and raise some pathogenic considerations.
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  • 17
    ISSN: 1432-2307
    Keywords: Keratin ; Mammary neoplasms ; Mouse ; Rat ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using immunoperoxidase staining of monoclonal antibody 312C8-1 against 51 000 dalton human keratin polypeptide, immunolocalization was observed in frozen sections of normal tissue and mammary tumours of adult female mice and rats. In normal tissue, the epitope was recognized in myoepithelial cells of the mammary, sweat and salivary glands, and in basal and suprabasal cells of the epidermis. However, the antibody did not react with luminal epithelial cells of the above glands or with mesenchymal cells. In spontaneous mammary tumours of mice, marker-positive tumour cells were distributed only in the outer layer of adenocarcinoma Type A, while they were scattered in some foci of adenocarcinoma Type B, and encircled the epithelial foci of pregnancy dependent tumours (plaque). All layers of epidermoid structures in adenoacanthoma revealed positivity. In rat mammary tumours induced by local dusting with 7, 12-dimethylbenz(α)anthracene (DMBA) powder, the staining pattern of benign tumours was comparable to that of the normal mammary gland. But, in addition to basally situated cells, marker-positive tumour cells were found scattered in the foci of adenocarcinoma, and were not restricted to basal cells in squamous cell carcinoma. The marker was not found in sarcomatous tissue. This antibody can therefore also be applied to rodents, and the staining pattern can be used to identify the epithelial subclass specific marker in normal tissue and in mammary tumours.
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  • 18
    ISSN: 1432-0738
    Keywords: 2,4-Dichlorophenoxyacetic acid ; Biogenic amines ; Brain ; Cerebrospinal fluid ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of single subcutaneous doses of sodium 2,4-dichlorophenoxyacetate (2,4-D-Na) on biogenic amines and their acidic metabolites in rat brain and cerebrospinal fluid (CSF) were analyzed by high pressure liquid chromatography. After 200 mg/kg 2,4-D-Na, the cerebral concentration of 5-hydroxytryptamine (5-HT) was increased slightly and that of 5-hydroxyindoleacetic acid (5-HIAA) roughly 3-fold between 1 and 8 h after the administration. There was also a tendency towards slightly lowered dopamine (DA) levels. No statistically significant changes in brain concentrations of noradrenaline (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) or tryptophan (TRY) were found. At the same time, however, the maximal increase in DOPAC, HVA and 5-HIAA concentrations in the CSF was 2.3–5.8-fold. The dependency of biogenic amines and metabolites on 2,4-D-Na dose was studied by injecting s.c. 0, 10, 30 and 100 mg/kg and sacrificing the rats at 2 h. In the brain, there was a dose-dependent increase in concentrations of 5-HIAA (at the two highest doses) and HVA (at the highest dose) while in the CSF those of all three acidic metabolites increased at the two highest doses. The 10 mg/kg dose had no effect. The results agree with the hypothesis that 2,4-D inhibits the organic acid transport out of the brain, which should then result in increased cerebral levels of acidic metabolites of biogenic amines, but it may also have effects on the activity of serotoninergic and dopaminergic neurones.
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  • 19
    ISSN: 1432-1351
    Keywords: Rat ; Melatonin ; Circadian rhythm ; 5-hydroxytryptophan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The rhythm in melatonin production in the rat is driven by a circadian rhythm in the pineal N-acetyltransferase (NAT) activity. Rats adapted to an artificial lighting regime of 12 h of light and 12 h of darkness per day were exposed to an 8-h advance of the light-dark regime accomplished by the shortening of one dark period; the effect of melatonin, triazolam and fluoxetine, together with 5-hydroxytryptophan, on the reentrainment of the NAT rhythm was studied. In control rats, the NAT rhythm was abolished during the first 3 cycles following the advance shift. It reappeared during the 4th cycle; however, the phase relationship between the evening rise in activity and the morning decline was still compressed. Melatonin accelerated the NAT rhythm reentrainment. In rats treated chronically with melatonin at the new dark onset, the rhythm had already reappeared during the 3rd cycle, in the middle of the advanced night, and during the 4th cycle, the phase relationship between the evening onset and the morning decline of the NAT activity was the same as before the advance shift. In rats treated chronically with melatonin at the old dark onset or in those treated with melatonin 8 h, 5 h and 2 h after the new dark onset during the 1st, 2nd and 3rd cycle, respectively, following the advance shift, the NAT rhythm reappeared during the 3rd cycle as well but in the last third of the advanced night only. Neither triazolam nor fluoxetine together with 5-hydroxytryptophan administered around the new dark onset facilitated NAT rhythm reentrainment after the 8-h advance of the light-dark cycle.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 413 (1989), S. 217-224 
    ISSN: 1432-2013
    Keywords: Rat ; Kidney ; Uptake ; Transport ; α-Ketoglutarate ; Luminal ; Basolateral ; Production
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to establish the characteristics of net renal transport and utilization of α-ketoglutarate (α-KG) in the rat, we have precisely quantified the renal blood flow, the urinary flow and the rates of α-KG delivery, filtration, reabsorption or secretion, excretion, uptake or production by an in vivo rat kidney preparation. In normal rats, α-KG uptake was higher than α-KG reabsorption at both endogenous and elevated plasma α-KG concentrations; thus, a net peritubular transport, which was the main supplier of α-KG to the renal cells, took place. Saturation of reabsorption and peritubular transport of α-KG occurred at blood α-KG concentrations about 30 and 150 times above normal, respectively. Acute metabolic acidosis was found to have no effect on renal handling of α-KG. At endogenous plasma α-KG concentrations, alkalosis converted net renal uptake into net renal production of α-KG resulting in addition of α-KG by the renal cells both to blood and to the luminal fluid. Elevation of blood α-KG concentration restored the renal uptake of α-KG. This uptake, which was entirely accounted for by the peritubular transport of α-KG, reached a maximum which was lower than that observed in normal and acidotic rats.
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  • 21
    ISSN: 1432-2013
    Keywords: Rat ; Skeletal muscle ; Development ; Ionic conductances ; Denervation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The development of membrane ionic conductances of rat extensor digitorum longus (EDL) muscle fibers was studiedin vitro using intracellular recordings. At 7–8 days after birth, the potassium conductance (GK) dominated the total membrane conductance while the chloride conductance (GC1) was very low. A rapid increased of GC1 towards adult values was observed after few days (12–14 day old rats), whereas GK did not decrease up to day 23. Denervation at 7–8 days after birth suppressed the maturation of the electrical parameters measured, and 15 days after the nerve crush, GC1 was just detectable. These results suggest that the maturation of the electrical properties, and in particular that of the resting chloride conductance in mammalian striated muscle fibers, occurs during the first weeks of postnatal life and is dependent on innervation.
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  • 22
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    Journal of cancer research and clinical oncology 115 (1989), S. 47-52 
    ISSN: 1432-1335
    Keywords: Alkylation ; Alkyl guanines ; Pancreas DNA ; Nitrosamines ; Acinar cells ; Duct cells ; Hamster ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activation of 3H-labeled N-nitrosobis(2-oxopropyl)amine ([3H]BOP) by pancreas acinar and duct tissue from Syrian hamsters and MRC-Wistar rats in vitro was measured as DNA alkylation. Hamster tissue was incubated with [3H]BOP (0.1 mM; 20 μCi/ml) for 2 h. Initial levels of alkylation were similar, 41.7±3.7 (acinar) and 51.5±7.8 (duct) dpm/μg DNA. Alkylation persisted for longer in duct (t/2〉46 h) than in acinar tissue (t/2=6 h). The faster repair of alkylation in acinar tissue was not due to acinar cell death. In rat duct tissue the level of alkylation 2 h after incubation (38.9±4.5 dpm/μg DNA) was similar to that in hamster ducts but declined more rapidly (t/2=27 h). Hamster and rat acinar and duct tissue was incubated with BOP followed by [3H]thymidine to measure DNA synthesis. BOP stimulated DNA synthesis in hamster but not in rat duct tissue or hamster acinar tissue. These data support the hypothesis that the duct tissue is the target tissue for BOP in Syrian hamsters.
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  • 23
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    Archives of gynecology and obstetrics 244 (1989), S. 151-155 
    ISSN: 1432-0711
    Keywords: Placenta ; Glycogen ; Triglyceride ; Cold ; Fasting ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of exposure to cold (+2°C, 3 and 24 h) and fasting (1, 2 and 3 days) on placental glycogen and triglyceride content was investigated in rats pregnant for 20 days. The stimuli did not affect the level of glycogen in the placenta. The level of triglycerides remained unchanged in the rats exposed to cold. It rose after only one day of fasting and then levelled out on the 2nd and 3rd days. Fasting, but not exposure to cold produced hypoglycemia and elevation of the plasma free fatty acids level. We conclude that activation of the adrenergic system during exposure to cold does not interfere with the glycogen and triglyceride content of the placenta. Prolonged hypoglycemia also does not affect the placental glycogen level although it increases the accumulation of neutral fat.
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  • 24
    ISSN: 1432-1106
    Keywords: α-melanocyte ; stimulating hormone ; Dopamine receptors ; Rat ; Hypothalamus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Release of alpha-melanocyte-stimulating hormone (α-MSH) from slices of rat hypothalamus superfused with artificial cerebro-spinal fluid (ACSF) was quantified by radioimmunoassay. Addition of 10-6 M quinpirole, a D2-dopamine receptor agonist, to the superfusion medium caused a significant (P 〈 0.001) reduction in the amount of α-MSH released upon depolarisation with 50 mM potassium from 319 ±37% to 110 ±16% of basal release in normal ACSF (mean ±S.E.M.). Basal peptide release in the presence of quinpirole was unaffected. Sulpiride, a D2-dopamine receptor antagonist, at a concentration of 10-6 M, induced a significant (P 〈 0.05) increase of both basal and potassium-stimulated α-MSH release to 203 ±21% and 447 ±88% of basal release in normal ACSF respectively. The latter increases were abolished when sulpiride and quinpirole were added in combination. SK&F 38393-A and SCH 23390, a D1-dopamine agonist and antagonist respectively, had no significant effect on either basal or potassiumstimulated α-MSH release. It is proposed that endogenous dopamine exerts an inhibitory control on α-MSH release from the rat hypothalamus via D2-dopamine receptors and that in isolated hypothalamic slices there is a tonic inhibition of peptide release due to the activity of this system.
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  • 25
    ISSN: 1432-1106
    Keywords: Collateral sprouting ; Nerve regeneration ; Mechanoreceptors ; C-fibers ; Plasma extravasation ; Evans blue ; Skin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The capacity of the saphenous nerve for collateral sprouting was examined by electrophysiological recordings of the activity of low threshold mechanoreceptors and plasma extravasation after C-fiber stimulation in rats. When the sciatic nerve was sectioned neonatally or in adults little evidence was obtained for collateral sprouting of either mechanoreceptors or fibers involved in plasma extravasation in the intact saphenous nerve0 In rats where the sciatic nerve was sectioned and the saphenous nerve was crushed either neonatally or in adults, expansive regenerative reinnervation by thin fibers, but not mechanoreceptors, was observed particularly in glabrous skin. Saphenous crush alone did not cause expansive regenerative reinnervation. The results indicate that much of the collateral sprouting or regenerative reinnervation of the skin observed in morphological studies may represent the presence of fibers not responding to the stimuli used in the present study. It is also suggested that some observations of collateral sprouting may represent changes in responsiveness to stimulation of skin areas with overlapping innervation territories.
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  • 26
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    Experimental brain research 76 (1989), S. 141-152 
    ISSN: 1432-1106
    Keywords: Abducens motoneurones ; Intracellular recordings ; HRP staining ; Membrane properties ; Somato-dendritic organization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The electrical and morphological properties of abducens motoneurones were investigated in the rat with intracellular recordings and intracellular HRP-staining. Motoneurones were identified by their antidromic response to electrical stimulation of the lateral rectus muscle. The antidromic action potential was followed by a delayed depolarization and an after hyperpolarization lasting 20 ms to 45 ms. The whole neurone input resistance (RN) calculated from I/V curves, was found to lie between 2 MΩ and 15 MΩ with a bimodal distribution (mean values 4.9 MΩ and 12 MΩ). In some cases, anomalous rectification was observed with low current intensities. Prolonged hyperpolarizing current pulses revealed the presence of a time dependant inward rectification and slow rebound depolarization. The intensity/frequency curves suggest the existence of three ranges of discharge. The average intensity frequency slope during the steady state was 43 imp/s/ nA. Eight abducens motoneurones were intracellularly labelled with HRP and fully reconstructed. The soma (23 μm to 40 μm in diameter) gave off 5 to 7 primary dendrites. The general organization and extension of the dendritic trees depended on the location of the soma within the abducens nucleus. The mean diameter of primary dendrites was 4.17 μm with similar average values in all motoneurones. The soma size of abducens motoneurones was not correlated with either the size of the proximal tree or the whole neurone input resistance.
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  • 27
    ISSN: 1432-1106
    Keywords: Parvalbumin ; GABA ; Nonpyramidal cell ; Monoclonal antibody ; Lectin ; Cerebral cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monoclonal antibody VC1.1 is shown to stain selectively a subpopulation of GABAergic neurons in the rat cerebral cortex. Almost all VC1.1 immunoreactive cells were also GABA-like immunoreactive (GABA-LI) and parvalbumin (PV) immunoreactive, whereas they were about 30% and 65% of GABA-LI and PV-positive cells in the parietal cortex and about 13% and 32% in the occipital cortex, respectively. Although a few VC1.1 positive cells showed somatostatinlike and/or cholecystokinin-like immunoreactivities, they were exceptional (less than 1% of VC1.1 positive cells). Furthermore about 90% of VC1.1 positive cells were also stained with a lectin, Vicia villosa agglutinin, with a specific affinity for terminal N-acetylgalactosamine.
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  • 28
    ISSN: 1432-1106
    Keywords: Inhibition ; Hippocampal formation ; Development ; GABAergic neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glutamate decarboxylase (GAD)-positive and Golgi impregnated local circuit neurons of the hippocampal formation of five day old rats were examined in light and electron microscopic preparations. The ultrastructural features of these neurons were similar in both the dentate gyrus and CA1 area of Ammon's horn. Somata displayed a perikaryal cytoplasm rich in organelles but lacked organized Nissl bodies. Most nuclei showed intranuclear infoldings of varying degrees but no intranuclear sheets or rods were found. Somata and dendrites were contacted by relatively immature axon terminals that formed mainly symmetric synapses. The axons of local circuit neurons in both the dentate gyrus and Ammon's horn formed symmetric synapses with somata and dendrites of the principal neurons in these regions. Thus, both GAD-positive and Golgi-impregnated terminals of local circuit neurons were observed to form synapses with pyramidal and granule cells. These terminals were usually small and contained relatively few pleomorphic synaptic vesicles. The results show that a circuitry for inhibition is established in the 5 day old dentate gyrus and Ammon's horn, even though the local circuit neurons lack some of the typical adult ultrastructural features at this age.
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  • 29
    ISSN: 1432-1106
    Keywords: Steroid receptor ; CRF ; Neurotensin ; Enkephalin ; CCK ; PHI ; VIP ; Somatostatin ; TRH ; Dopamine ; Immunohistochemistry ; Arcuate nucleus ; Hormones ; Neurosecretion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The paraventricular nucleus (PVN) of male albino rats was analyzed for the presence of glucocorticoid receptor-like immunoreactivity (GR-LI) in neuropeptide containing neurons. Using immunohistochemistry, coronal sections trough the entire PVN were double-stained with a mouse monoclonal antibody against GR and one of the following antisera: rabbit antiserum to corticotropin releasing factor (CRF), neurotensin (NT), enkephalin (ENK), cholecystokinin (CCK), thyrotropin releasing hormone (TRH), galanin (GAL), peptide histidine isoleucine (PHI), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) or tyrosine hydroxylase (TH). For comparison the occurrence of GR-LI in NT-, SOM-, NPY- or TH-positive neurons of the arcuate nucleus was also studied. Our results indicate that GR-LI is present in the parvocellular part of the PVN but not in its magnocellular portion. Virtually every parvocellular neuron in the PVN containing one of the above mentioned peptides was also positive for GR, with the exception of SOM neurons, of which only about two thirds showed detectable levels of GR-LI. All TH-positive, presumably dopamine neurons in the PVN were GR-positive. In the arcuate nucleus all TH- and NPY-positive neurons as well as a large proportion of the SOM- and NT-immunoreactive neurons contained GR-LI. The results indicate that in the PVN, in addition to the CRF neurons, certain peptidergic neurons in the parvocellular part of the PVN, without any established role in the control of ACTH synthesis and release, may also be under glucocorticoid control. This seems to be the case also for most arcuate neurons.
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  • 30
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    Experimental brain research 78 (1989), S. 164-173 
    ISSN: 1432-1106
    Keywords: Glia ; GFAP ; Brainstem ; Spinal cord ; Immunocytochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The topographical mapping of glial fibrillary acidic protein (GFAP)-immunoreactivity was performed in coronal serial sections of the rat mesencephalon, rhombencephalon and spinal cord. Relative to a background of poor or moderate overall staining of the mesencephalon, the interpeduncular nucleus, substantia nigra and the periaqueductal grey matter were prominent by their intense GFAP-immunoreactivity. The pons and particularly the medulla contained more GFAP-labelled elements compared with the mesencephalon. The spinal trigeminal nucleus and Rolando substance were distinguished by their intense staining. Large fibre tracts were usually poor in immunoreactive GFAP. In a concluding discussion, findings relevant to the GFAP-mapping of the whole rat CNS are evaluated with regard to possible reasons underlying the observed differential distribution of GFAP-immunoreactivity.
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  • 31
    ISSN: 1432-1106
    Keywords: Cardiopulmonary vagal reflex ; Bezold-Jarisch reflex ; Excitatory amino acid ; Caudal ventrolateral medulla ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The importance of the caudal ventrolateral medulla (CVLM) in mediating vagal cardiopulmonary (Bezold-Jarisch reflex) reflex activity was studied in urethane-anaesthetized rats. Unilateral electrolytic lesion of the CVLM markedly attenuated Bezold-Jarisch reflex responses (hypotension and bradycardia) elicited by intravenous injections of 5-HT. Bilateral lesion of the CVLM virtually abolished the reflex responses. Microinjection of the excitatory amino acid (EAA) receptor antagonist kynurenate (KYN), but not the inactive analogue xanthurenate, into the CVLM markedly attenuated the reflex responses to 5-HT. The N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 also markedly attenuated reflex activity. Furthermore, lesions, KYN and MK-801 all tended to elevate resting blood pressure and to reduce resting heart rate. These findings support the hypothesis that the CVLM is an important medullary locus mediating cardiovascular reflex integration and that an EAA synapse in the CVLM is important in the cardiopulmonary reflex arc.
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  • 32
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    Experimental brain research 78 (1989), S. 214-218 
    ISSN: 1432-1106
    Keywords: Nigral grafts ; Adrenal grafts ; Rotation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Separate groups of rats with unilateral 6-OHDA lesions of the nigrostriatal pathway received intrastriatal foetal (E14) substantia nigra suspension grafts, intrastriatal postnatal (P22–25) adrenal medulla suspension grafts using either collagenaseor trypsin-based dissociation procedures, intraventricular adrenal medulla grafts, or remained with lesions alone. Rats with nigral or adrenal suspension grafts, but not rats with adrenal solid grafts, showed reduced apomorphine-induced rotation in comparison with lesion rats. The nigral graft group alone showed substantial reduction of amphetamine-induced rotation, and this was the only group manifesting good long-term graft survival. These results indicate that nigral and adrenal grafts do not have comparable mechanisms of functional action, and suggest that adrenal grafts can ameliorate apomorphine-induced rotation by a non-specific mechanism.
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  • 33
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    Experimental brain research 78 (1989), S. 233-242 
    ISSN: 1432-1106
    Keywords: Hoppocampus ; Granule cells ; Long lasting inhibition ; Frequency habituation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In paired pulse stimulation experiments the mechanism underlying frequency habituation of postsynaptic potentials in dentate granule cells of rat hippocampal slices was studied by measuring extra and intracellular potentials as well as changes in extracellular calcium ([Ca2+]0) and potassium concentrations ([K+]0). Orthodromic stimulation of the perforant path induced in most granule cells a late, slow hyperpolarization (SH), lasting for up to 1.2 s. During the SH the membrane conductance was increased by up to 40%. The reversal potential of the SH was around -90 mV and varied with the [K+]0. Frequency habituation was seen in all cells with the SH, whereas cells which display frequency potentiation had no SH. Lowering of [Ca2+]0 reversed paired pulse induced frequency habituation into frequency potentiation at [Ca2+]0 levels where the SH disappeared. Phaclofen blocked the SH and reversed frequency habituation into frequency potentiation. Elevating [Mg2+]0 also reversed frequency habituation into frequency potentiation and reduced the SH. We conclude that the SH represents a late, slow IPSP which is responsible for frequency habituation in dentate granule cells. We noted that during repetitive stimulation the SH soon started to fade. This effect can in part be attributed to extracellular K+-accumulation as suggested by the K+-dependence of the slow IPSP and the observations of changes in [K+]0 during repetitive stimulation. This could explain why frequency habituation reverses into frequency potentiation during repetitive stimulation.
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  • 34
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    Experimental brain research 76 (1989), S. 646-650 
    ISSN: 1432-1106
    Keywords: Glutamate binding sites ; Autoradiography ; Vestibular nuclei ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Quantitative autoradiography has been used to characterize l-[3H] glutamate binding sites and to describe their distribution in frozen sections of rat vestibular nuclei. Scatchard plots and Hill coefficients of glutamate binding suggest that glutamate interacts with a single population of sites having a KD of about 126 nM and a capacity of 2.5 pmol/mg of protein. Although the level of glutamate binding was not very high compared to the highest levels described for some other brain regions, it was nonetheless substantial. The sites were distributed unevenly in the four vestibular nuclei and their distribution correlated well with the projection areas of the vestibular nerve, which has been described as a glutamate-mediated pathway. The highest numbers of glutamate binding sites were observed in the medial vestibular nuclei. This technique provides a very sensitive assay for characterizing the pharmacological subtypes of glutamate binding in the vestibular nuclei and for analyzing changes in these sites during development or after deafferentation of the vestibular nuclei.
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  • 35
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    Experimental brain research 76 (1989), S. 656-661 
    ISSN: 1432-1106
    Keywords: Central chemoreceptor ; Carbon dioxide ; Nucleus tractus solitarius ; Nucleus ambiguus ; Cardiopulmonary control ; Brain slice ; Intracellular recording ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To identify central sites of potential CO2/H+-chemoreceptive neurons, and the mechanism responsible for neuronal chemosensitivity, intracellular recordings were made in rat tissue slices in two cardiopulmonary-related regions (i.e., nucleus tractus solitarii, NTS; nucleus ambiguus, AMBc) during exposure to high CO2. When the NTS was explored slices were bisected and the ventral half discarded. Utilizing such “dorsal” medullary slices removed any impinging synaptic input from putative chemoreceptors in the ventrolateral medulla. In the NTS, CO2-induced changes in firing rate were associated with membrane depolarizations ranging from 2–25 mV (n = 15). In some cases increased e.p.s.p. activity was observed during CO2 exposure. The CO2-induced depolarization occurred concomitantly with an increased input resistance ranging from 19–23 MΩ (n = 5). The lower membrane conductance during hypercapnia suggests that CO2-induced depolarization is due to a decreased outward potassium conductance. Unlike neurons in the NTS, AMBc neurons were not spontaneously active and were rarely depolarized by hypercapnia. Eleven of 12 cells tested were either hyperpolarized by or insensitive to CO2. Only 1 neuron in the AMBc was depolarized and it also showed an increased input resistance during CO2 exposure. Our findings suggest that CO2/H+-related stimuli decrease potassium conductance which depolarizes the cell and increases firing rate. Although our in vitro studies cannot guarantee the specific function of these cells, we believe they may be involved with brain pH homeostasis and cardiopulmonary regulation.
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  • 36
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    Experimental brain research 74 (1989), S. 41-46 
    ISSN: 1432-1106
    Keywords: Cortico-cortical neurons ; Sensorimotor cortex ; Glutamate and aspartate immunoreactivity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Retrograde transport of tracers and immunocytochemistry have been used to determine if association and callosal neurons in the primary motor and somatosensory cortex of rats contain high levels of glutamate or aspartate and may, thus, use these amino acids as neurotransmitter. After tracer injections in these areas, about 65% of the retrogradely labeled neurons in layer V in the ipsilateral or contralateral hemisphere are immunopositive for glutamate. Lower percentages of double-labeled neurons are found in layers III, VI, and II. Similar results are obtained when sections are processed for aspartate immunoreactivity. About 90% of retrogradely labeled neurons are immunopositive in sections incubated with a mixture of both glutamateand aspartate antisera. These results suggest that a large fraction of cortico-cortical neurons are immunoreactive for either one amino acid but not for both. It is proposed that neurons with high levels of one amino acid use this as neurotransmitter; high levels of glutamate and aspartate are likely to be present in a fraction of neurons which may release both amino acids or a substance closely related to these.
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  • 37
    ISSN: 1432-1106
    Keywords: Extincton ; Nonreward ; Adrenoceptor ; Noradrenaline ; Stress ; Sympathetic nervous system ; 6-hydroxydopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We tested whether the stress of nonreward has neurochemical effects on noradrenergic neurones which resemble those reported for other forms of stress. Rats trained to run in a straight runway for food reward were subjected to either 1 or 10 extinction trials. Half the rats in each group were injected before the start of acquisition with IP 6-hydroxydopamine to deplete peripheral noradrenaline stores. All animals were killed immediately after their final test in the runway, together with untrained controls. Noradenaline depletion had no behavioural or neurochemical effects. The rate of extinction in the 10-trial group, which was indexed by the slope of the linear regression of running time on trial, correlated negatively with both alpha2 and beta-adrenoceptor number (Bmax). There were no differences between groups in cerebral cortical noradrenaline content, or alpha2 or beta-adrenoceptor binding. These results substantially conflict with those predicted from Stone's hypothesis relating beta-adrenoceptor sensitivity to the behavioural response to stress. A further finding was that alpha2, but not beta-adrenoceptor number, negatively correlated with levels of noradrenaline in the tissue, suggesting that noradrenaline is less involved in the regulation of beta than in that of alpha2-adrenoceptors.
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  • 38
    ISSN: 1432-1106
    Keywords: Caudate-putamen ; Neural plasticity ; Nigrostriatal projection ; Sensory deprivation ; Vibrissae ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of unilateral removal of vibrissae on the crossed and uncrossed nigrostriatal projections was examined with the horseradish peroxidase tract tracing technique. Hemivibrissotomy mainly affected the projections arising from the rostral part of the substantia nigra. One to three days after clipping the vibrissae, rats were found to have more labeled neurons in the crossed projection to the caudate-putamen (CPU) on the same side as vibrissae removal than in the crossed projection to the CPU opposite to vibrissae removal. A reversed asymmetry was seen in rats examined 4–20 days after vibrissae removal. These animals had more labeled cells in the crossed and uncrossed projections terminating in the CPU opposite to the shaved side, i.e. in the hemisphere deprived of vibrissal sensory input. This time-course of neural alterations is similar to that of the recovery from behavioral asymmetries seen after hemivibrissotomy. Similar time-dependent alterations in the nigrostriatal projection had been found after unilateral injection of 6-OHDA into the substantia nigra.
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  • 39
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    Experimental brain research 77 (1989), S. 499-506 
    ISSN: 1432-1106
    Keywords: Temporal/entorhinal area ; Memory processing ; Neurotransmitters ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of the present study was to investigate whether effects of temporo-entorhinal disconnections on acquisition and retention of a visual discrimination task might be associated with neurochemical dysfunctions. The results revealed that the present lesions impaired both acquisition and retention of the discrimination task. This impairment was accompanied by decreased glutamergic activity in both temporal and entorhinal cortices. No changes were seen in levels of acetylcholine or GABA. Further, the distribution of glutamate/ aspartate was related to both regional and hemispheric differences. The results are discussed in terms of a highly integrative role of the lateral entorhinal cortex and in terms of other putative neurotransmitter systems involved in the function of memory.
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  • 40
    ISSN: 1432-1106
    Keywords: Ventrobasal thalamic neurones ; Noxious mechanical stimulation ; Orofacial receptive fields ; Trigeminal sensory complex ; Tractotomy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Single units were recorded, using extra-cellular glass microelectrodes, in the ventrobasal complex of the thalamus of rats under halothane-nitrous oxide anaesthesia. The animals had previously undergone a large bilateral section of the trigeminal sensory complex just above the obex to deprive the caudal part of the trigeminal sensory complex (subnucleus caudalis) of its trigeminal afferents. As observed on frontal slices our lesions impaired the whole descending tract and, in most cases, the intratrigeminal pathways between the rostral and the caudal part of the complex. Forty-seven units responding to a somatic mechanical noxious stimulation applied to the trigeminal area were recorded in these conditions. Forty-two of these had a receptive field (or at least a part of it) in or around the oral and nasal cavities, and 5 in the peripheral part of the face. These data confirm the hypothesis that the rostral part of the trigeminal sensory complex participates in pain sensory pathways, as a first relay site between nociceptive primary afferents coming from oral, perioral and perinasal areas, and the ventrobasal complex of the thalamus. In addition, they suggest that the intra-trigeminal pathways are not essential for the transmission of these nociceptive inputs, to the lateral thalamus.
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  • 41
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    Psychopharmacology 97 (1989), S. 35-39 
    ISSN: 1432-2072
    Keywords: Delta-sleep-inducing peptide (DSIP) ; Paradoxical sleep (PS) ; Phosphorylated analogue of DSIP ; Rat ; Sleep substance ; Slow wave sleep (SWS)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Continued 10-h nocturnal intracerebroventricular infusion of 0.5 nmol P-DSIP, the phosphorylated analogue of delta-sleep-inducing peptide (DSIP), significantly increased slow wave sleep (22%) and paradoxical sleep (81%) in unrestrained rats. The increase in the amount of sleep was largely due to an increase in the number of sleep episodes. Larger and smaller doses were ineffective in doses ranging from 0.025 to 25 nmol. The sleep-promoting potency of P-DSIP was 5 times greater than that of DSIP compared by the same assay.
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  • 42
    ISSN: 1432-2072
    Keywords: Thermoregulation ; Acetylcholine ; Muscarinic ; Serotonin ; Interaction ; Alaproclate ; Oxotremorine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Stimulation of muscarinic cholinergic receptors with the highly potent and selective receptor agonist oxotremorine produced hypothermia in rats. Alaproclate, a purported selective serotonergic reuptake inhibitor, potentiated this response. Destruction of central presynaptic serotonergic terminals with the potent cytotoxin p-chloroamphetamine (PCA) failed to attenuate the hypothermic response to oxotremorine in alaproclate-pretreated animals. These results could be taken to suggest that alaproclate may act, at least in part, via a non-serotonergic mechanism to potentiate the oxotremorine-induced hypothermic response.
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  • 43
    ISSN: 1432-2072
    Keywords: Feeding ; 5-HT antagonists ; 5-HT1 receptors ; 5-HT1C receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of nine central 5-HT antagonists on food intake in free feeding male rats were examined. The 5-HT2 antagonists ritanserin and ketanserin and the selective 5-HT3 antagonists ICS 205-930 and MDL 72222 had no effect on food intake. In contrast, the non-selective 5-HT antagonists metergoline, methiothepin, mesulergine, mianserin and methysergide (all of which have high affinity for various 5-HT1 receptor subtypes), dose-dependently increased food intake during a 4-h daytime test. Furthermore, metergoline dose dependently increased food intake over a 24-h period. Suprisingly, mesulergine decreased food intake over a 24-h period at the same doses that increased daytime food intake. This may indicate that the increase in daytime feeding produced by mesulergine is a non-specific response. Although the antagonists used have varying degrees of selectivity for 5-HT receptor subtypes, the pattern of results suggests that postsynaptic 5-HT1 receptors (possibly of the 5-HT1C type) play an important role in the control of feeding in rats.
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  • 44
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    Psychopharmacology 97 (1989), S. 175-178 
    ISSN: 1432-2072
    Keywords: Serotonin ; Morphine ; Nicotine ; Amphetamine ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of two potent and specific antagonists of 5HT3 receptors, ICS 205-930 and MDL 72222, on the reinforcing properties of amphetamine, morphine and nicotine was studied in rats. Durg-induced reinforcement was assessed by measuring drug-conditioned place preference. ICS 205-930 and MDL 72222 dose-dependently reduced the place preference induced by morphine (1.0 mg/kg SC). At doses of 0.030 mg/kg SC the two antagonists completely blocked morphine-induced place preference while doses of 0.015 mg/kg SC significantly reduced it. ICS 205-930 and MDL 72222 at doses of 0.030 mg/kg SC also prevented the place preference induced by nicotine (0.6 mg/kg SC). In contrast, ICS 205-930 and MDL 72222 up to doses of 0.030 mg/kg SC failed to modify the place preference elicited by amphetamine (1.0 mg/kg SC). The results indicate that 5HT3 receptors are specifically involved in the reinforcing properties of morphine and nicotine.
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  • 45
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    Psychopharmacology 97 (1989), S. 206-212 
    ISSN: 1432-2072
    Keywords: LSD-cue ; Drug discrimination ; Risperidone ; Schizophrenia ; 5-HT2-catecholamine antagonism ; LSD antagonism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Risperidone was studied in a 0.16 mg/kg LSD-saline drug discrimination test procedure. At doses varying from 0.0025 to 0.63 mg/kg, no LSD-like agonist effects were observed. Studies on the antagonism of the LSD-cue indicated that risperidone was able to completely block the discriminative stimulus properties of LSD with a minimum ED50-value of 0.028 mg/kg. Risperidone was also very active over time with reference to LSD antagonism, the ED50s after 2, 4 and 8 h pretreatment being 0.028, 0.064 and 0.44 mg/kg. Response rate reductions were only observed at doses ≧0.16 mg/kg after 1 h and at 0.63 mg/kg after 2 h pretreatment. Four and 8 h after treatment, no rate-reducing effects were apparent at doses up to 2.50 mg/kg. Thus at pretreatment intervals ranging between 2 and 8 h, complete antagonism of LSD without any rate effects was obtained. As compared to other LSD antagonists, risperidone was quantitatively better than setoperone and ritanserin and longer acting than pirenperone. Based on the pharmacological profile of risperidone and the other LSD antagonists, it was concluded that a potent central 5-HT2 and catecholamine antagonism is needed for a potent and complete antagonism of the 0.16 mg/kg LSD-cue. The potential clinical effect of risperidone in the positive and negative symptoms of schizophrenia is discussed.
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  • 46
    ISSN: 1432-2072
    Keywords: Rat ; Operant behavior ; Fixed-interval ; Ventral tegmental area ; Neurotensin ; Substance P ; Neurokinin-α (substance K) ; d-Ala-Met-enkephalin ; Dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The neuropeptides neurotensin, substance P, neurokinin-α (substance K), and met-enkephalin are present endogenously in the ventral tegmental area (VTA), site of the A10 dopaminergic (DA) cell bodies. In the present study these four peptides were injected bilaterally into the VTA in the rat, and the effects on operant behavior were assessed. Cannulae aimed at the VTA were implanted in four groups of animals, which had been trained to bar-press for food reward on a fixed-interval, 40-s schedule. A fifth group, in which the effects of systemically administered amphetamine were assessed, was also tested. Response rate across the interval was measured, and the index of quarter-life was taken as an indication of the temporal pattern of resonding. In addition, a rate-dependency analysis was carried out for all data. Neurotensin (NT, 0.0175, 0.175, 0.5 μg in 1 μl) dose-dependently decreased response rates without affecting quarter-life, and reduced the number of reinforcements obtained. Substance P (SP, 0.1, 1.0, 3.0 μg) did not affect responding, and neurokinin-α (NKA, 0.1, 1.0, 3.0 μg) induced a small increase in responding. Quarter-life was not affected by SP or NKA, but responding on the nonreinforced lever was significantly increased by both peptides. d-Ala-met-enkephalin (DALA, 0.01, 0.1, 1.0 μg) induced a dose-dependent increase in responding which was also rate-dependent, and reduced quarter-life. DALA effects were similar to the classic pattern of responding observed after systemic amphetamine. These results suggest that although all these peptides elicit behavioral activation and may affect DA neuronal activity, the behavioral responses can be differentiated with respect to operant behavior.
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  • 47
    ISSN: 1432-2072
    Keywords: Social memory ; Cholinomimetic drugs ; Nootropic drugs ; Benzodiazepine inverse agonists ; Psychostimulants ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The recognition of an unfamiliar juvenile rat by an adult rat has been shown to imply short-term memory processes. In this study the effect of various psychotropic drugs on this investigatory behaviour was examined. The procedure was as follows: an unfamiliar juvenile rat was placed in the home cage of an adult rat for 5 min. The time spent by the adult rat in investigating the juvenile was recorded. The adult rat was then immediately treated with vehicle or test compounds, and was again exposed for 5 min to the same juvenile 2 h later. At this time point vehicle-treated rats no longer recognized the juvenile rat, i.e. the time of investigation was similar to that observed during the first presentation. Arecoline (1 and 3 mg/kg IP), physostigmine (0.05 and 0.1 mg/kg SC), RS86 (0.5 mg/IP) and nicotine (0.125 and 0.5 mg/kg IP) reduced in a dose-dependent fashion the time spent in investigating the juvenile during the second exposure. This result cannot be attributed to nonspecific effects, since it was not observed when a different juvenile was used for the second exposure. The effect of arecoline was reversed by scopolamine, but not by methylscopolamine. Aniracetam reduced investigatory behaviour at the dose of 50 mg/kg IP. FG 7142 (5 mg/kg IP) and β-CCM (0.4 mg/kg IP) were also active and their effect was reversed by Ro 15-1788. dl-Amphetamine (0.5 and 1 mg/kg IP), nomifensine (1.25–10 mg/kg IP) and strychnine (0.25 and 0.5 mg/kg IP) were ineffective or reduced this behaviour unspecifically. Social recognition may therefore represent a useful and simple test to detect compounds which enhance short-term, olfactory, memory and to assess in the same animals the specificity of this activity.
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  • 48
    ISSN: 1432-2072
    Keywords: Penile erection ; Yawning ; Hypophysectomy ; Monosodium glutamate ; Oxytocin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Penile erection and yawning induced by the intracerebroventricular (ICV) injection of oxytocin (10–1000 ng) was studied in hypophysectomized rats and in rats neonatally treated with monosodium glutamate (MSG), a treatment that depletes hypothalamic opiomelanocorticotropinderived peptides without altering their pituitary and circulating concentration. Oxytocin effect was strongly reduced by hypophysectomy, but not by neonatal MSG. Testosterone replacement (50 μ/kg/day for 23 days) partially reversed the effect of hypophysectomy on penile erection, but not on yawning. The present results suggest that oxytocin does not induce penile erection and yawning by releasing an ACTH-derived peptide from hypothalamic opiomelanotropinergic neurons, and that the pituitary gland exerts a permissive role on the expression of the above behavioural responses induced by oxytocin.
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  • 49
    ISSN: 1432-2072
    Keywords: Sleep ; 5-Hydroxytryptamine (5-HT) ; Antagonist ; Agonist ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently developed agents specifically acting on different 5-hydroxytryptamine (5-HT) receptor populations were used to analyze the functional role of 5-HT2 receptor subtypes in the sleep-wakefulness cycle of the rat. The 5-HT2 receptor antagonist ritanserin injected intraperitoneally (IP) (0.04–2.5 mg/kg) induced an increase in deep slow wave sleep (SWS2) duration at the expense of wakefulness (W), light slow wave sleep (SWS1) and paradoxical sleep (PS). The stimulation of 5-HT2 receptors by 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced a dose-related increase in W and a dose-dependent decrease in both SWS2 and PS. Pretreatment with ritanserin (0.16–2.5 mg/kg) or with cinanserin (2.5–5 mg/kg), another 5-HT2 receptor antagonist, dose-dependently reversed the W enhancement and the SWS2 deficit produced by DOM, but not the PS deficit. Sleep-wakefulness alterations (increase in W and SWS1 combined with a suppression of SWS2 and PS) observed after IP injection of two putative 5-HT1 receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (2.5 mg/kg) and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969) (0.63 mg/kg), were not modified by ritanserin pretreatment (0.16–2.5 mg/kg). These results further support the hypothesis that the serotonergic system plays an active role in the regulation of the sleep-wakefulness cycle in the rat and that 5-HT2 receptors are involved in this action. In addition it is suggested that 5-HT1 receptor subtypes are unlikely to interact with 5-HT2 receptors in the sleep-wakefulness modulation mediated through 5-HT2 receptors.
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  • 50
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    Psychopharmacology 97 (1989), S. 466-470 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Benzodiazepine ; Midazolam ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats (N=12) were trained to discriminate midazolam (1 mg/kg, IP) from vehicle in a food reinforced operant conditioning procedure. Midazolam, flunitrazepam, diazepam, chlordiazepoxide and pentobarbital showed dose-dependent substitution for midazolam. Buspirone and Ro 15-1788 did not substitute for midazolam. The midazolam cue was dose-dependently antagonized by Ro 15-1788. In rats (N=12) trained to discriminate chlordiazepoxide (3 mg/kg, IP) from vehicle midazolam, flunitrazepam, diazepam and chlordiazepoxide substituted completely and dose dependently for chlordiazepoxide. The relative potency of chlordiazepoxide and diazepam was three times less in the midazolam-trained animals than in the chlordiazepoxide-trained animals. Response rate and latency data further support the main finding that the midazolam cue is similar, but not identical to the cue of classical benzodiazepines.
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  • 51
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    Psychopharmacology 97 (1989), S. 521-528 
    ISSN: 1432-2072
    Keywords: Trimethyltin ; Delay conditioning ; Conditioned flavor aversion ; Passive avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Trimethylin (TMT) produces behavioral and cognitive deficits resulting, in part, from limbic system toxicity. To determine whether these effects result from learning deficits or accelerated memory loss, the present experiment examined two delay conditioning paradigms in rats previously treated with either saline or TMT. Saline-treated Long-Evans rats receiving injections of lithium after consuming saccharin-flavored water later avoided saccharin ingestion: the degree of avoidance varied inversely with the time (0.5, 3 or 6 h) separating initial saccharin availability and lithium injection. Rats treated with TMT (8 mg/kg IV, 30 days prior) showed impaired conditioning at the long but not the short or intermediate delay conditions, suggesting that the deficits were mnemonic and not associative. Similar delay-dependent deficits in rats treated with TMT were observed in a passive avoidance task that arranged one of two delays between response emission and shock delivery during training. The effects of TMT on delay conditioning were accompanied by reduced bodyweight and hippocampal pathology. In summary, TMT appears to alter the temporally dependent association of events (entering darkened compartment versus saccharin consumption) and consequences (foot shock versus lithium administration) during acquisition. Furthermore, the observed deficits in delay conditioning produced by TMT did not appear to be task specific, with similar effects determined with tests of both somatosensory and gustatory avoidance learning designed to distinguish between functional alterations due to deficits in memorial processes from those due to altered sensory, motor, or associative processes.
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  • 52
    ISSN: 1432-2072
    Keywords: Amygdala ; Benzodiazepine ; GABA ; Barbiturates ; Conflict ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to elucidate the role of the amygdala in rat conflict behavior in a water lick suppression test, we examined the effect of lesions of various nuclei of the amygdaloid complex on this behavior. An anticonflict effect was produced by a lesion of the anterior part of central and basolateral amygdala, and lesion to the posterior part of the central amygdala, but not by posterior of the basolateral amygdala or medial amygdala lesions. These results suggest that the amygdala, especially the anterior part of the central and basolateral nuclei, plays an important role in conflict behavior of rats in the water lick test. In a second experiment, the effects of benzodiazepine- and GABA-antagonists on the anticonflict action of diazepam, zopiclone, and phenobarbital injected into the anterior part of central and basolateral amygdala were examined, also using a water lick suppression test. A dose-dependent anticonflict action was produced by systemic administration as well as by intra-amygdala injection of diazepam, zopiclone, lormetazepam, flurazepam and phenobarbital. The order of potency was lormetazepam〉zopiclone≧diazepam〉flurazepam ≧phenobarbital for both routes of injection. The antiamygdala effects of diazepam and zopiclone injected into the amygdala were completely reversed by Ro15-1788 and β-CCM but not by bicuculline, while the anticonflict effect of phenobarbital was reversed by β-CCM but not by Ro15-1788 or bicuculline. The present results strongly suggest that the anterior nuclei of central and basolateral amygdala are important sites of action of antianxiety drugs, and that an anticonflict action produced by intra-amygdala injection of benzodiazepines or barbiturate is mediated through the different receptor mechansims.
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  • 53
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    Psychopharmacology 98 (1989), S. 61-67 
    ISSN: 1432-2072
    Keywords: Rat ; Place preference ; Extinction ; Conditioning ; Naloxone ; Heroin ; Clonidine ; Pimozide ; Memory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These experiments examined the neurochemical mechanisms involved in the development and expression of place conditioning produced by heroin. Conditioned place preferences (CPP) lasting up to 8 weeks were obtained with doses of 50–1000 μg/kg heroin, using a regimen shown not to produce physical dependence. Naloxone pretreatment (50 μg/kg) during conditioning prevented the acquisition of heroin-induced CPP, but when given only on the test day, naloxone (50 or 1000 μg/kg) did not prevent the expression of heroin CPP. Clonidine disrupted the establishment of heroin CPP at 20 μg/kg, but disrupted its expression only at debilitating doses (100 and 200 μg/kg). Pimozide attenuated the acquisition (100 μ/kg) and expression (250 μg/kg) of heroin CPP. Together, these results support a role for opioid and catecholamine systems in the acquisition of heroin reinforcement, but they suggest that once heroin CPP is established, its expression in opiate-free subjects is not opiate receptor mediated and is relatively refractory to pharmacological treatments which disrupt acquisition. The data challenge the notion that the conditioned effects of opiates in drug-free animals are related to the release of endogenous opioids, and they also may help to explain why naloxone and clonidine are ineffective in the treatment of opiate addiction.
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  • 54
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    Psychopharmacology 98 (1989), S. 203-206 
    ISSN: 1432-2072
    Keywords: Place conditioning ; Motivation ; Aversion ; Opioids, μ-, δ- and κ-receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of central versus peripheral opioid receptors in mediating the aversive effects of opioids was examined by use of an unbiased place preference conditioning procedure in rats. The non-selective opioid antagonist naloxone (NLX) produced conditioned aversions for the drug-associated place after subcutaneous (SC) as well as intracerebroventricular (ICV) administration. Place aversions were also observed in response to the ICV administration of the selective μ-antagonist CTOP. In contrast, the selective δ-antagonist ICI 174,864 and the selective κ-antagonist norbinaltorphimine (nor-BNI) (ICV) were without effect. Place aversions were also produced by central applications of the selective κ-agonist U50,488H and the dynorphin derivative E-2078. For those opioid ligands tested, the doses required to produce place aversions were substantially lower following ICV as compared to SC administration. These data confirm that κ-agonists and opioid antagonists produce aversive states in the drug-naive animal and demonstrate that this effect is centrally mediated. Furthermore, the ability of NLX and CTOP, in contrast to both ICI 174,864 and nor-BNI, to produce place aversions suggests that the aversive effects of opioid antagonists result from the blockade of μ-receptors.
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  • 55
    ISSN: 1432-2072
    Keywords: LY 163502 ; Dopamine D-1 and D-2 receptors ; Jerking ; Behavioural assessment ; Stereotypy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The new, extremely potent and enantioselective D-2 agonist LY 163502 failed to induce compulsive stereotyped behaviour. Very low doses (3–6 μg/kg) inhibited spontaneous sniffing and locomotion, while higher doses (12–50 μg/kg) induced episodes of non-stereotyped sniffing and chewing; these actions showed complete enantioselectivity. Up to 200-fold higher doses modestly induced only locomotion. Responsivity to LY 163502 was enantioselectively blocked by the selective D-2 antagonist R-piquindone. This responsivity was also enantioselectively blocked by the selective D-1 antagonist R-SK&F 83566 but, additionally, episodes of atypical limb/body jerking behaviour were released; thus, LY 163502 induced such jerking only when tonic D-1 activity was suppressed. These data extend our notion that there may be at least two forms of functional interaction between D-1 and D-2 receptor systems: one cooperative, as in the regulation of typical sniffing, and another oppositional, as in the regulation of atypical jerking.
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  • 56
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    Psychopharmacology 98 (1989), S. 286-288 
    ISSN: 1432-2072
    Keywords: IP pirenzepine ; Passive avoidance ; Brain penetration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract When injected IP, the M1 muscarinic receptor antagonist pirenzepine dose-dependently induced a deficit in passive avoidance learning in rats. This activity was optimal at 75 mg/kg injected 1 h before the acquisition session. The deficit induced by pirenzepine was antagonized by oxotremorine (0.03–0.3 mg/kg SC) and physostigmine (0.1 mg/kg SC), but not neostigmine. By comparison, under the same experimental conditions, physostigmine and oxotremorine also antagonized the deficit induced by an equipotent dose of scopolamine (0.5 mg/kg IP), although the activity of physostigmine appeared stronger against scopolamine than against pirenzepine. These results suggest that pirenzepine could produce a centrally-mediated behavioural disruption when injected systemically.
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  • 57
    ISSN: 1432-2072
    Keywords: Hallucinogenics ; Amphetamine ; Rat ; Tele-Stereo-EEG
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Telemetric recordings of field potentials from frontal cortex, hippocampus, striatum and reticular formation of freely moving rats were analysed before and after injection of the enantiomeric hallucinogenic amphetamine derivatives R-DOB [(−)-1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane], R-DOM [(−)-1-(2,5-dimethoxy-4-methylphenyl)-2-amino-propane] and R-DOI [(−)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropanel] as well as the nonhallucinogenic amphetamine derivatives S-MBDB [(+)-N-methyl-1-(1,3-benzodioxol-5-yl)butanamine] and S-MDMA [(+)-3,4-methylenedioxymethamphetamine] and S-(+)-amphetamine. The frequency analysis of the field potentials revealed a clearcut difference between them. The spectral patterns emerging after injection of the non-hallucinogens were characterized by a general decrease of power, the changes in the alpha2 and delta band being the most prominent, whereas only after the application of the hallucinogenic compounds was a contrasting increase of power observed in the alpha1 frequency band, especially in the striatum. As increases in alpha1 power have been correlated in the same pharmacological model to serotonergic control mechanisms, the results are in line with the hypothesis that 5-HT2 receptors, predominantly occurring in the striatum, might be involved in the hallucinogenic action of drugs.
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  • 58
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    Psychopharmacology 98 (1989), S. 412-416 
    ISSN: 1432-2072
    Keywords: Adrenoceptors ; Behaviour ; Noradrenaline ; Open field ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were injected IP once daily for 14 consecutive days with propranolol (5 mg/kg), yohimbine (2.5 mg/kg) or saline vehicle. A fourth group was unhandled during this time. Each rat was then placed in an open field for 4 min and its activity and defaecation recorded. Immediately after this, the animals were killed and cerebral cortices removed for radioligand binding to α2- and β-adrenoceptors and measurement of noradrenaline content. We report two sets of findings. First, β-adrenoceptor density correlated positively, and affinity negatively, with the number of movements towards the centre of the field in the final 3 min of the trial. α2-Adrenoceptor K d, in contrast, correlated both with movements around the field and those directed towards the centre. Secondly, whereas the only specific drug effect was an increase in defaecation after treatment with propranolol, β-adrenoceptor density was increased and affinity decreased in all injected groups, suggesting a non-specific effect of the stress of injection. Movements to and from the centre of the field were also increased in injected groups during the first minute of the trial. In both sets of findings the association of β-adrenoceptor density with greater resistance to stress is hard to reconcile with existing theories of the role of β-adrenoceptors in behavioural responses to stress.
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  • 59
    ISSN: 1432-2072
    Keywords: Haloperidol ; Dopamine ; Oral movements ; Rat ; Tardive dyskinesia ; Homovanillic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats with more severe orofacial movements after 51 days of haloperidol administration showed lower levels of the dopamine metabolite homovanillic acid (HVA) in the caudate compared to animals who did not develop significant mouth movements. This effect was not observed in other brain regions sampled. This finding is consistent with the hypothesis that dopaminergic receptor supersensitivity in neostriatal structures plays some role in the development of orofacial movements in rats, in association with chronic neuroleptic administration.
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  • 60
    ISSN: 1432-2072
    Keywords: SCH 23390 ; Catalepsy ; Tolerance ; Neuroleptics ; Rat ; Chronic treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The development of tolerance to the cataleptic effect of the selective D-1 antagonist SCH 23390 (0.5 mg/kg/day SC or 0.1 mg/kg/day SC) and haloperidol (1 mg/kg/day SC) during repeated administration was investigated. Catalepsy in rats was measured using the horizontal bar method. SCH 23390 induced a dose-related cataleptic effect of short duration, whereas the cataleptic effect of haloperidol appeared more slowly and lasted longer. Marked tolerance to the cataleptic effect of haloperidol developed already 6 days from the beginning of the treatment. The cataleptic effect of the higher dose regimen of SCH 23390 was also significantly reduced after 6 days' treatment. However, unlike haloperidol, this subacute tolerance was gradually reversed and was no longer significant after 12 and 18 days. The cataleptic response to the lower dose of SCH 23390 (0.1 mg/kg/day) was not significantly altered during the treatment and no initial catalepsy tolerance was observed with this dose regimen. These results suggest that different mechanisms are involved in the expression of cataleptic behaviour during chronic treatment with SCH 23390 and classical antipsychotics, such as haloperidol.
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