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.
RCT Entities:
RATIONALE: The endogenous GABAergic neuroactive steroid3alpha-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.
Authors: Martin Hill; Petr Popov; Helena Havlikova; Lyudmila Kancheva; Jana Vrbikova; Milan Meloun; Radmila Kancheva; David Cibula; Vladimir Pouzar; Ivan Cerny; Luboslav Starka Journal: Alcohol Clin Exp Res Date: 2005-06 Impact factor: 3.455
Authors: E Romeo; A Ströhle; G Spalletta; F di Michele; B Hermann; F Holsboer; A Pasini; R Rupprecht Journal: Am J Psychiatry Date: 1998-07 Impact factor: 18.112
Authors: Laura E O'Dell; Ahmed A Alomary; Monique Vallée; George F Koob; Robert L Fitzgerald; Robert H Purdy Journal: Eur J Pharmacol Date: 2004-01-26 Impact factor: 4.432
Authors: Remco W M Zoethout; Wilson L Delgado; Annelies E Ippel; Albert Dahan; Joop M A van Gerven Journal: Br J Clin Pharmacol Date: 2011-03 Impact factor: 4.335
Authors: Amira Pierucci-Lagha; Jonathan Covault; Richard Feinn; Rahul T Khisti; A Leslie Morrow; Christine E Marx; Lawrence J Shampine; Henry R Kranzler Journal: Psychopharmacology (Berl) Date: 2005-12-10 Impact factor: 4.530
Authors: Patrizia Porcu; Todd K O'Buckley; Sarah E Alward; Soomin C Song; Kathleen A Grant; Harriet de Wit; A Leslie Morrow Journal: Alcohol Clin Exp Res Date: 2009-12-17 Impact factor: 3.455
Authors: Ahmet Sait Hasirci; Antoniette M Maldonado-Devincci; Matthew C Beattie; Todd K O'Buckley; A Leslie Morrow Journal: Alcohol Clin Exp Res Date: 2017-01-09 Impact factor: 3.455
Authors: P Porcu; A M Barron; C A Frye; A A Walf; S-Y Yang; X-Y He; A L Morrow; G C Panzica; R C Melcangi Journal: J Neuroendocrinol Date: 2016-02 Impact factor: 3.627
Authors: Jonathan Covault; Timothy Pond; Richard Feinn; Albert J Arias; Cheryl Oncken; Henry R Kranzler Journal: Psychopharmacology (Berl) Date: 2014-02-21 Impact factor: 4.530