EFFECTS OF BENZODIAZEPINE AGONIST EXPOSURE ON CORTICOTROPIN-RELEASINGFACTOR CONTENT AND HORMONAL STRESS RESPONSES - DIVERGENT RESPONSES INMALE AND OVARIECTOMIZED FEMALE RATS

Benzodiazepine agonists affect endocrine responses of the hypothalamic -pituitary-adrenal axis and can antagonize many of the actions of cort icotropin-releasing factor (CRF). Gender and gonad-related factors can influence both the development of tolerance to the benzodiazepines in rats and the concomitant neural adaptations associated with chronic b enzodiazepine agonist exposure. This study compared changes in CRF con tent, corticosterone release and ACTH levels after diazepam exposure i n ovariectomized female (OVX) and male rats, After treatment with diaz epam for 3 days (acute) or 3 weeks (chronic), content of CRF immunorea ctivity in eight brain areas and serum corticosterone were determined by radioimmunoassay in handling-habituated rats. The effects of acute and chronic benzodiazepine exposure on swim stress-induced corticoster one and ACTH release were also examined. Chronic diazepam exposure red uced stress-induced corticosterone and ACTH release in OVX, but not ma le, rats. Acute diazepam exposure similarly attenuated stress-induced corticosterone release in OVX rats, but did not affect ACTH release. O VX control groups had greater levels of CRF than males in several brai n regions. Gender-specific alterations in CRF content after chronic di azepam exposure were observed in amygdala, locus ceruleus and median e minence. Chronic benzodiazepine agonist exposure increased CRF levels in the amygdala of OVX rats, but not males. Both chronic and acute dia zepam exposure increased CRF content in the locus ceruleus of male, bu t not OVX, rats. These results indicate that the effects of benzodiaze pine exposure on neural CRF systems are region specific and influenced by gender-related factors.