Moderate doses of ethanol fail to increase plasma levels of neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one-like immunoreactivity in healthy men and women.

RATIONALE The endogenous GABAergic neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP, allopregnanolone) has been proposed to contribute to ethanol actions. Humans synthesize 3alpha,5alpha-THP, but its role in response to systemic administration of ethanol is unclear. OBJECTIVE The present study aims to determine the effect of a moderate dose of ethanol on progesterone and 3alpha,5alpha-THP concentrations in plasma samples of healthy male and female subjects and to determine if these levels are related to the subjective effects of ethanol. Females were tested in both the follicular and luteal phases of the menstrual cycle. METHODS Healthy men (N=9) and women (N=12) aged 21-35 participated in the study. Men participated in two sessions on which they received ethanol (0.8 g/kg) or placebo. Women participated in four sessions on which they received ethanol (0.7 g/kg) or placebo during the follicular and luteal phases of their cycle. Subjective states and mood were measured by standardized self-report questionnaires and a measure of psychomotor performance. Steroid levels (progesterone, 3alpha,5alpha-THP, estradiol, and cortisol) were measured in plasma samples by radioimmunoassay. RESULTS Ethanol significantly increased plasma levels of progesterone, but not 3alpha,5alpha-THP-like immunoreactivity, in women in the luteal phase. Ethanol had no effect on progesterone or 3alpha,5alpha-THP-like immunoreactivity levels in women in the follicular phase or in men, and it did not increase cortisol in men or women. Ethanol also did not affect estradiol in men or women. CONCLUSIONS 3alpha,5alpha-THP-like immunoreactivity levels in human plasma are not increased following moderate ethanol consumption, suggesting that circulating levels of progesterone or its tetrahydro-reduced metabolites do not play a major role in ethanol action. However, the possibility remains that ethanol increases endogenous brain production of GABAergic neurosteroids without affecting plasma levels. Moreover, humans synthesize 5beta-reduced GABAergic steroids, and levels of these steroids may be altered in plasma or brain.