Abstract
Previous investigations have found gender differences in the effects of chronic ethanol exposure on ethanol withdrawal behaviors as well as GABA A receptor 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 assessment of ethanol withdrawal anxiety behaviors were found. However, the neuroactive steroid, 3α,5α-THP, increased exploratory behavior in ethanol withdrawn female, but not male, rats. GABA A receptor binding assays showed potent competition of [ 35S]TBPS binding by 3α,5α-THP. Control females displayed a decreased affinity for 3α,5α-THP compared to control males, as evidenced by a nearly 30% increase in the IC 50 value. There was no significant effect of ethanol withdrawal on 3α,5α-THP modulation of [ 35S]TBPS binding. However, gender differences were observed in the effects of chronic ethanol exposure on GABA A receptor subunit peptide levels in the hypothalamus. Female rats had a significant increase in peptide levels for the α2 and α3 but not α4 subunit, whereas male rats displayed a significant increase in α4 and α3 but not α2 subunits compared to pair-fed control levels. Chronic ethanol-induced alterations in gene expression in the hypothalamus did not coincide with previous findings in the cerebral cortex. In particular, male rats showed an increase in α1 subunit peptide levels in the hypothalamus, whereas significant decreases in this subunit have been observed in the cerebral cortex. Both female and male rats showed significant increases in the α3 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.
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