Ovariectomy has minimal effects on neuroadaptations associated with ethanol dependence in female rats

We previously found gender selective alterations in gene expression for GAB A(A) and NMDA receptors associated with the development of ethanol dependen ce. Males and females have a differing hormonal environment, including ster oid hormone derivatives (neuroactive steroids) that exert effects at GABA(A ) and NMDA receptors. Therefore, we explored whether the removal of ovarian steroids would alter gender differences in response to chronic ethanol exp osure. We found that ovariectomy reduced ethanol drinking levels by 15%, co mparable to earlier observations between intact female and male rats. Howev er, investigation of the effects of chronic ethanol exposure on intact vers us ovariectomized female rats uncovered few differences in chronic ethanol- induced alterations in selected GABA(A) or NMDA receptor subunit peptide le vels. In general, findings for both groups of females were similar to previ ous observations. There was no reduction in GABA(A) receptor alpha 1 subuni t levels in cerebral cortex in either intact or ovariectomized female rats, in contrast to the significant reduction observed in male rats. In additio n, both intact and ovariectomized female rats had increased levels of the N MDA NR1 subunit in cerebral cortex and hypothalamus, but not in hippocampus , whereas ethanol dependent male rats displayed significant increases in th e NR1 subunit only in hippocampus. Radioligand binding analysis with [S-35] TBPS found no differences in modulation of the GABA(A) receptor by neuroact ive steroids between ethanol dependent male, intact female or ovariectomize d female rats. Seizure susceptibility was not different between intact or o variectomized female rats during ethanol withdrawal. We did observe differe ntial effects on brain allopregnanolone and plasma corticosterone levels be tween ethanol dependent intact and ovariectomized female rats, suggesting t hat ovarian steroids influence HPA axis adaptations to prolonged ethanol ex posure. Overall, these data suggest that ovarian steroids do not significan tly impact the gender selective alterations of GABA(A) and NMDA receptors a ssociated with ethanol dependence. (C) 2000 Elsevier Science Ltd. All right s reserved.