摘要:

PREVIOUS studies suggested the involvement of the neuronal nitric oxide synthase (nNOS) in the development of sensitization to psychostimulants. In the present study we investigated the role of nNOS in the rewarding properties of cocaine. Swiss Webster mice treated with cocaine (20 mg/kg) and saline every other day for 8 days (four drug and four saline sessions) developed conditioned place preference (CPP) for the drug-paired compartment of the cage. Pretreatment with the nNOS inhibitor, 7-nitroindazole (7-NI; 25 mg/kg), completely blocked cocaine-induced CPP. Mice deficient for the nNOS gene (homozygote nNOS(−/−) mice) were resistant to cocaine-induced CPP, while wild-type nNOS(+/+) mice developed a marked CPP following cocaine administration. Both, the pharmacological and genetic manipulations of nNOS suggest that nitric oxide (NO) is involved in the rewarding properties of cocaine.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

MAINTENANCE of long-term potentiation in perforant path-granule cell synapses is accompanied by increased glutamate release. Here we investigate the role of synaptophysin in release and in expression of long-term potentiation in dentate gyrus. We report that long-term potentiation was accompanied by increased endogenous glutamate release and increased tyrosine phosphorylation of synaptophysin, but these changes were attenuated when long-term potentiation was inhibited by the tyrosine kinase inhibitor tyrphostin AG879 or by the NMDA antagonist D-aminophosphonovalerate. In vitro analysis revealed that KCl-induced glutamate release was abolished in synaptosomes prepared in the presence of antisynaptophysin. The data suggest a role for synaptophysin in release and indicate that activation of tyrosine kinase and synaptophysin phosphorylation contribute to long-term potentiation perhaps by modulating glutamate release.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

SURPRISINGLY, we observed that nerve growth factor (NGF) potentiated death of PC12 cells induced by glucose withdrawal, although NGF is widely believed to exert its protective role against several types of cell death. Since either glucose withdrawal or NGF treatment increases intracellular calcium levels of target cells in many cases, we hypothesized that further increase of intracellular calcium by NGF may be a determinant factor in the NGF-mediated cell death. To test this hypothesis, we examined the effect of NGF on cell death pharmacologically by measuring cell viability and traced the changes of intracellular calcium in various conditions using a confocal laser microscope. NGF promoted cell death under a glucose-deprived condition in a manner dependent on extracellular calcium, and nifedipine, but not ryanodine, could partially block the cell death. NGF treatment augmented further intracellular calcium that had been elevated by glucose withdrawal, the event that nifedipine could block. In this study, therefore, we tentatively concluded that NGF potentiates cell death of starved PC12 cells by accelerating the initial increase of intracellular calcium through activation of a dihydropyridine-sensitive calcium channel.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

TA20 is a cDNA clone which was previously reported to encode a novel neuronal differentiation factor. However, the majority of this clone has near perfect DNA sequence homology with cytochrome b mitochondrial sequence and an additional 5′ region which lacks homology with any previously reported sequence. Furthermore, careful study of the library construction method indicates that the full length TA20 clone is likely an artifact arising from the head-to-head blunt-ended ligation of two unrelated cDNAs. Thus, the effects on growth and neurite outgrowth observed in correlation with the overexpression of TA20 in neuronal cells, as well as its mRNA distribution in the developing rat brain require further study.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

THE distribution of 5-HT2Areceptor immunoreactivity in the brain stem was studied by means of a commercial 5-HT2Amouse monoclonal antibody against the N-terminal portion of the receptor (amino acids 1–72). The 5-HT2Aimmunoreactivity demonstrated in the nerve terminal or dendritic-like structures of regions of the nucleus raphe pallidus, nucleus interfascicularis, motor nucleus of the trigeminal nerve, the ventral and dorsal tegmental nuclei and the median eminence by means of double immunofluorescence procedures were shown to be associated with 5-HT immunoreactive cell body-dendritic and/or nerve terminal structures. Besides synaptic transmission the relationships are compatible with the existence of short distance volume transmission (in the mm range) in 5-HT2Amediated 5-HT communication through terminal (5-HT)-terminal (5-HT2A) or soma/dendro (5-HT)-terminal (5-HT2A) and terminal (5-HT)-dendritic (5-HT2A) interactions in discrete brain stem nuclei.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

WE have shown that neurons from embryonic chick ciliary ganglia in primary culture possess receptors for insulin-like growth factor I (IGF-I). When added to serum- and insulin-free culture medium, the factor potently enhanced neuronal survival as observed after 24 and 48 h of culture. The effect saturated at 5 ng/ml. Laminin was not necessary for the trophic effects of IGFI; in the absence of the factor, it had no effect on neuronal survival. Insulin exerted a trophic effect similar to that observed with IGF-I, but at higher doses. The trophic effect of IGF-I was sharply and specifically reduced when either a membrane-permeable calcium chelating agent or blockers of voltage-dependent calcium channels were added to the medium.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

IT has been hypothesized that endogenous glucocorticoids represent an important negative feedback system involved in the modulation of cytokine-induced fever through the inhibition of prostaglandins (PG) production in the preoptic anterior hypothalamus (AH/POA). The purpose of this study was to determinate whether glucocorticoids modulate the PG-independent febrile response induced by macrophage inflammatory protein-1β (MIP-1β) in a manner similar to other pyrogenic cytokines. Subcutaneous pretreatment with dexamethasone (1, 2 and 4 mg/kg; 1 h) had no effect on fever induced by microinjection of 50 pg MIP-1β into the rat's AH/POA. It is demonstrated for the first time that, unlike other cytokines, fever induced by MIP-1β is independent of glucocorticoid modulation. Finally, these results offer new perspectives about the pathogenesis of glucocorticoid-unresponsive pyrexia.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

SEVERAL lines of work demonstrate that there are two subtypes of k opioid receptors. Intrathecally administered agonists for the k1subtype are not effective in treating pain, whereas agonists for the k2receptor are anti-hyperalgesic and anti-allodynic. The question addressed here was whether the ratio of spinal k1to k2receptors was conserved across species. Thus, binding experiments were performed on spinal cord membranes from rats, guinea pigs, monkeys and humans. We found that k2receptors were approximately ten times more abundant than k1receptors in all species tested. This suggests that the anti-hyperalgesic and anti-allodynic properties of k2agonists may also be conserved. Therefore, selective k2agonists may be effective in treating chronic pain in humans.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

POSITRON emission tomography (PET) studies have shown normal or elevated levels of glucose metabolism in neuronal heterotopia, raising the issue of potential participation of heterotopic neurons in cognitive processing. We studied three patients with heterotopic malformations, using [15O]water PET and experimental conditions selected according to the location of the malformations. Task performance was associated with blood flow increases of > 17% within the heterotopia in each patient. In two, these occurred in left frontal heterotopia during sentence generation. In the third patient, activations for facial and visuospatial discrimination and picture naming were found in a right posterior heterotopion. Our findings may reflect participation of heterotopia in cognitive function and suggest that heterotopic neurons synapse with neurons in other brain regions.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

TO test the role of 5-HT1Areceptors in the action of antidepressants, we investigated the effect of chronic paroxetine (10 mg/kg, p.o. for 21 days) on functional assays of 5-HT1Asensitivity. We constructed cumulative concentration response curves to the selective 5-HT1Aagonist (+)-8-OH-DPAT on both extracellular recordings of 5-HT neurones and electrically stimulated 5-HT release in dorsal raphe brain slices. Chronic paroxetine desensitized the 5-HT1Areceptors controlling firing, with an increase in EC50from 10.7 nM to 46.2 nM 8-OH-DPAT. Chronic paroxetine did not, however, desensitize the 5-HT1Areceptors controlling 5-HT release but increased the 8-OH-DPAT Emaxfrom 54.9% to 79.2% inhibition of 5-HT release. These data suggest that there are either two distinct populations of 5-HT1Areceptors or separate second messenger systems, one controlling 5-HT release and another influencing firing. Furthermore chronic paroxetine treatment can differentially modulate these different populations.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID