Search resultsModerate doses of ethanol fail to increase plasma levels of neurosteroid 3α-hydroxy-5α-pregnan-20-one-like immunoreactivity in healthy men and women
Title
Moderate doses of ethanol fail to increase plasma levels of neurosteroid 3α-hydroxy-5α-pregnan-20-one-like immunoreactivity in healthy men and women
Publication type
Journal Article
Year of Publication
2006
Authors
Journal
Psychopharmacology
Volume
186
Issue
3
Pagination
442 - 450
Date published
2006
ISBN
00333158 (ISSN)
Keywords
3alpha hydroxy 5alpha pregnan 20 one, 3α,5α-THP, Adult, alcohol, alcohol consumption, Allopregnanolone, article, blood sampling, controlled study, Estradiol, estradiol blood level, Ethanol, Female, follicular phase, GABAergic neuroactive steroids, GABAergic system, hormone blood level, hormone synthesis, human, human experiment, Humans, hydrocortisone, hydrocortisone blood level, Hypnotics and Sedatives, immunoreactivity, luteal phase, male, menstrual cycle, neurosteroid, normal human, placebo, Pregnanolone, priority journal, progesterone, psychomotor performance, questionnaire, radioimmunoassay, self report, standard, steroid, steroid blood level, Subjective
Abstract
Rationale: The endogenous GABAergic neuroactive steroid 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP, allopregnanolone) has been proposed to contribute to ethanol actions. Humans synthesize 3α,5α-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 3α,5α-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, 3α,5α-THP, estradiol, and cortisol) were measured in plasma samples by radioimmunoassay. Results: Ethanol significantly increased plasma levels of progesterone, but not 3α,5α-THP-like immunoreactivity, in women in the luteal phase. Ethanol had no effect on progesterone or 3α,5α-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: 3α,5α-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 5β-reduced GABAergic steroids, and levels of these steroids may be altered in plasma or brain.