Chronic ethanol drinking increases during the luteal menstrual cycle phase in rhesus monkeys: implication of progesterone and related neurosteroids
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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.
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.
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.
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.
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.
KeywordsMenstrual cycle Luteal phase Alcohol Female Progesterone Monkey Neurosteroid Self-administration
The authors would like to thank Kevin Nusser for his expertise in animal training, Christa Helms for statistical analysis, Steve Gonzales for development of drinking panels and data analyses, the Endocrine Technology Support Core at the Oregon National Primate Research Center for assaying serum progesterone, and Aleksandr Salo for statistical and graphic contributions.
This study was funded by AA013510, AA13641, AA109431 (KAG and EJB), OD11092, AA012439 (DAF) and facilities and resources at the VA Portland Health Care System (DAF).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Clark JR, Dierschke DJ, Wolf RC (1978) Hormonal regulation of ovarian folliculogenesis in rhesus monkeys: concentrations of serum luteinizing hormones and progesterone during laparoscopy and patterns of follicular development during successive menstrual cycles. Biol Reprod 18(5):779–783CrossRefGoogle Scholar
- Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Erlbaum Associates, HillsdaleGoogle Scholar
- Finn DA, Jimenez VA (2018) Dynamic adaptation in neurosteroid networks in response to alcohol. Handb Exp Pharmacol. https://doi.org/10.1007/164_2017_82
- Finn DA, Purdy RH (2007) Neuroactive steroids in anxiety and stress. In: Sibley D, Hanin I, Kuhar M, Skolnick P (eds) Handbook of contemporary neuropharmacology. John Wiley & Sons, New Jersey, pp 133–176Google Scholar
- Magden ER, Mansfield KG, Simmons JH, Abee CR (2015) Nonhuman Primates. In: Fox JG et al (eds) Laboratory animal medicine, 3rd edn. Elsevier, San Diego, p 799Google Scholar
- Marshall JC (2001) Hormonal regulation of the menstrual cycle and mechanisms of ovulation. In: DeGroot LJ, Jameson JL (eds) Endocrinology, 4th edn. WB Saunders, Philadelphia, pp 2073–2074Google Scholar
- National Research Council (2011) Guide for the care and use of laboratory animals, 8th edn. National Academies Press, Washington, D.C.Google Scholar
- Snelling C, Tanchuck-Nipper MA, Ford MM, Jensen JP, Cozzoli DK, Ramaker MJ, Helms M, Crabbe JC, Rossi DJ, Finn DA (2014) Quantification of ten neuroactive steroids in plasma in Withdrawal Seizure–Prone and –Resistant mice during chronic ethanol withdrawal. Psychopharmacology 231:3401–3414CrossRefGoogle Scholar
- Vivian JA, Green HL, Young JE, Majerksy LS, Thomas BW, Shively CA, Tobin JR, Nader MA, Grant KA (2001) Induction and maintenance of ethanol self-administration in cynomolgus monkeys (Macaca fascicularis): long-term characterization of sex and individual differences. Alcohol Clin Exp Res 25(8):1087–1097CrossRefGoogle Scholar
- Wilks JW, Hodgen GD, Ross GT (1979) Endocrine characteristics of ovulatory and anovulatory menstrual cycles in the rhesus monkey. In: Hafez ESE (ed) Human Ovulation. Elsevier, Amsterdam, pp 205–218Google Scholar