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Physiological doses of progesterone potentiate the effects of triazolam in healthy, premenopausal women

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Abstract

Rationale

Gender plays a critical role in the effects of drugs and drug abuse liability. Biological factors, including ovarian hormones, may contribute to gender differences in drug abuse. Preclinical and some clinical research suggests that progesterone and its metabolites have activity at the GABAA receptor and may enhance the effect of GABAergic compounds (e.g., benzodiazepines). Because women are exposed to varying levels of progesterone from puberty until menopause, and appear more sensitive to the negative consequences of benzodiazepine use, it is important to understand the impact of progesterone on GABAergic drug effects.

Objectives

The purpose of this experiment was to characterize the behavioral effects of progesterone, alone and in combination with the short-acting benzodiazepine, triazolam, to determine if progesterone potentiates the behavioral effects of triazolam.

Methods

Oral micronized progesterone (0, 100, and 200 mg) and oral triazolam (0.00, 0.12, and 0.25 mg/70 kg) were administered to healthy, premenopausal women (n = 11) under conditions of low circulating sex hormones. The subjective, performance and physiological effects of progesterone, alone and in combination with triazolam, were assessed.

Results

Triazolam alone produced prototypical sedative-like effects. Progesterone alone also engendered some sedative effects, although the time course of the effects was more limited than that of triazolam. Progesterone increased and extended the duration of triazolam effects and delayed the onset of triazolam peak effects, most notably at the 0.12 mg/70 kg dose.

Conclusions

Progesterone potentiates the behavioral effects of benzodiazepines and may contribute to benzodiazepine use and abuse among women.

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Acknowledgments

The authors wish to thank Stephanie LaBedz, Stephanie Douglas, Dustin Lee, Laura Mudd, Caroline Kimathi, Cleeve Emurian, Glenn Robbins, Phoebe Brown, and Beth Eaves for expert technical assistance. We also thank Steven Sitzlar of the University of Kentucky Investigational Drug Service.

This research and the preparation of this manuscript were supported by grants from the National Institute on Drug Abuse (R36 DA024127, T32 DA007304) and the Center for Biomedical Research Excellence (P20 RR015592). The authors do not have any financial relationship with these funding sources and have no conflict of interest to report.

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Authors and Affiliations

  1. Department of Behavioral Science, College of Medicine, University of Kentucky Medical Center, Lexington, KY, 40536-0086, USA

    Shanna Babalonis, Joshua A. Lile & Thomas H. Kelly

  2. Department of Psychiatry, University of Kentucky Medical Center, Lexington, KY, USA

    Catherine A. Martin & Thomas H. Kelly

  3. Department of Psychology, University of Kentucky College of Arts and Sciences, Lexington, KY, USA

    Shanna Babalonis & Thomas H. Kelly

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  1. Shanna Babalonis
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  2. Joshua A. Lile
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Correspondence to Shanna Babalonis.

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Babalonis, S., Lile, J.A., Martin, C.A. et al. Physiological doses of progesterone potentiate the effects of triazolam in healthy, premenopausal women. Psychopharmacology 215, 429–439 (2011). https://doi.org/10.1007/s00213-011-2206-7

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