Brain research
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In the present work we studied the relationship between behaviour in the forced swimming test (FST), a test that presumably measures depressive-like behaviour in rodents, and central corticotropin-releasing factor (CRF) concentration and binding in five strains of rats. The strains were: Brown-Norway (BN), Fisher (FIS) 344, Lewis (LEW), spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The FST data corresponding to the pretest showed significant inter-strain differences in both struggling and immobility: BN and WKY rats displayed lower levels of struggling and longer periods of immobility, LEW and SHR rats showed intermediate levels, and FIS rats were the most active. ⋯ The study of CRF content in various brain areas revealed inter-strain differences in prefrontal cortex and pons-medulla, but not in parietal-temporal cortex or in hypothalamus (CRF concentrations in the hippocampus were not detectable): CRF content in the prefrontal cortex was higher in BN than in the other strains, although the differences with FIS were not statistically significant; in the pons-medulla, FIS and LEW showed significantly higher CRF content than the other strains. From the present results it appears that BN and WKY rats were more prone to adopt passive strategies in the FST, but they did not show higher brain CRF immunoreactivity or down-regulation of CRF receptors. Hence, although there were inter-strains differences in all variables studied, no evidence for a relationship between the FST behaviour and central CRF activity was found.
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The neurotransmitter gamma-aminobutyric acid (GABA) exerts a tonic inhibitory influence on proopiomelanocortin (POMC) neurons in the hypothalamus as well as on the melanotrope cells of the intermediate lobe (IL) of the pituitary gland. Moreover, the activation of the GABAA receptor complex by different ligands has been shown to exert a negative influence on the POMC gene expression at the hypothalamic level. In order to elucidate the in vivo regulation of the POMC mRNA levels in the intermediate lobe of the pituitary by endogenous ligands of the GABAA receptor complex, we have studied the effect of intravenous (i.v.) and intracerebroventricular (i.c.v) injections of octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor (DBI). ⋯ On the other hand, MK-906 produced a decrease in mRNA levels and could not reverse the effect of ODN. The results indicate that activation of the GABAA receptor complex by the endogenous benzodiazepine receptor ligand ODN can induce a negative regulation of POMC gene expression in the IL of the pituitary and neurons in the AN. The present results do not provide clear evidence that neurosteroids are involved in the action of ODN on POMC gene expression in the IL.