Chronic ethanol drinking increases during the luteal menstrual cycle phase in rhesus monkeys: implication of progesterone and related neurosteroids

• Published in: Psychopharmacology Vol. 236; no. 6; pp. 1817 - 1828
• Main Authors: Dozier, Brandy L., Stull, Cara A., Baker, Erich J., Ford, Matthew M., Jensen, Jeremiah P., Finn, Deborah A., Grant, Kathleen A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2019; Springer; Springer Nature B.V
• Subjects: Alcohol; Alcohol use; Alcohol, Denatured; Alcohols; Biomedical and Life Sciences; Biomedicine; Drinking behavior; Drinking of alcoholic beverages; Ethanol; Menstrual cycle; Menstruation; Monkeys; Neurosciences; Neurosteroids; Original Investigation; Pharmacology/Toxicology; Progesterone; Psychiatry; Steroid hormones; Steroids; Variation; Self-administration; Luteal phase; Menstrual cycle; Monkey; Alcohol; Female; Neurosteroid; Progesterone
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-019-5168-9

Rationale Sporadic reports of alcohol consumption being linked to menstrual cycle phase highlight the need to consider hormonally characterized menstrual cycle phase in understanding the sex-specific effects of risk for alcohol drinking in women. Objectives We investigated the association between menstrual cycle phase, characterized by circulating progesterone and menses, with accurate daily alcohol intakes in rhesus monkeys, and the contribution of progesterone derived neuroactive steroids to cycle-related alcohol drinking. Methods Menses (daily) and progesterone (2–3×/week) were obtained in female monkeys ( n  = 8, 5 ethanol, 3 control) for 12–18 months. Ethanol monkeys were then induced to drink ethanol (4% w / v ; 3 months) and given 22 h/day access to ethanol and water for approximately 1 year. In selected cycles, a panel of neuroactive steroids were assayed during follicular and luteal phases from pre-ethanol and ethanol exposure. Results There were minimal to no effects of ethanol on menstrual cycle length, progesterone levels, and follicular or luteal phase length. The monkeys drank more ethanol during the luteal phase, compared to the follicular phase, and ethanol intake was highest in the late luteal phase when progesterone declines rapidly. Two neuroactive steroids were higher during the luteal phase versus the follicular phase, and several neuroactive steroids were higher in the pre- vs. post-ethanol drinking menstrual cycles. Conclusions This is the first study to show that normal menstrual cycle fluctuations in progesterone, particularly during the late luteal phase, can modulate ethanol intake. Two of 11 neuroactive steroids were selectively associated with the effect of cycle progesterone on ethanol drinking, suggesting possible links to CNS mechanisms of ethanol intake control.