Gender impacts behavioral and neurochemical adaptations in ethanol-dependent rats

Previous investigations have found gender differences in the effects of chr onic ethanol exposure on ethanol withdrawal behaviors as well as GABAA rece ptor gene expression. The present investigation extended these studies with additional behavioral and neurochemical measures of ethanol dependence and withdrawal. No significant gender differences in the elevated plus-maze as sessment of ethanol withdrawal anxiety behaviors were found. However, the n euroactive steroid, 3 alpha,5 alpha-THP, increased exploratory behavior in ethanol withdrawn female, but not male, rats. GABA(A) receptor binding assa ys showed potent competition of [S-35]TBPS binding by 3 alpha,5 alpha-THP. Control females displayed a decreased affinity for 3 alpha,5 alpha-THP comp ared to control males, as evidenced by a nearly 30% increase in the ICS, va lue. There was no significant effect of ethanol withdrawal on 3 alpha,5 alp ha-THP modulation of [S-35]TBPS binding. However, gender differences were o bserved in the effects of chronic ethanol exposure on GABA(A) receptor subu nit peptide levels in the hypothalamus. Female rats had a significant incre ase in peptide levels for the alpha 2 and alpha 3 but not alpha 4 subunit, whereas male rats displayed a significant increase in alpha 4 and alpha 3 b ut not alpha 2 subunits compared to pair-fed control levels. Chronic ethano l-induced alterations in gene expression in the hypothalamus did not coinci de with previous findings in the cerebral cortex. In particular, male rats showed an increase in oil subunit peptide levels in the hypothalamus, where as significant decreases in this subunit have been observed in the cerebral cortex. Both female and male rats showed significant increases in the alph a 3 subunit in the hypothalamus but not the cerebral cortex. Taken together , these studies provide additional support for gender-selective effects of chronic ethanol-elicited adaptations at the molecular level. (C) 1999 Elsev ier Science Inc.