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

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Abstract

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.

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Acknowledgements

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.

Funding

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).

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Authors and Affiliations

  1. Division of Comparative Medicine, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, OR, 97006, USA

    Brandy L. Dozier & Cara A. Stull

  2. Department of Computer Science, Baylor University, One Bear Place #97356, Waco, TX, 76798, USA

    Erich J. Baker

  3. Division of Neuroscience, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, OR, 97006, USA

    Matthew M. Ford & Kathleen A. Grant

  4. Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, 97239, USA

    Matthew M. Ford, Jeremiah P. Jensen & Deborah A. Finn

  5. Department of Research, VA Portland Health Care System, Portland, OR, 97239, USA

    Deborah A. Finn

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  1. Brandy L. Dozier
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Correspondence to Kathleen A. Grant.

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Dozier, B.L., Stull, C.A., Baker, E.J. et al. Chronic ethanol drinking increases during the luteal menstrual cycle phase in rhesus monkeys: implication of progesterone and related neurosteroids. Psychopharmacology 236, 1817–1828 (2019). https://doi.org/10.1007/s00213-019-5168-9

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  • DOI: https://doi.org/10.1007/s00213-019-5168-9

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