The influence of menstrual cycle phase on sensitivity to ethanol-like discriminative stimulus effects of GABA(A)-positive modulators

Kristen L. Green, Alexey V. Azarov, Kendall T. Szeliga, Robert H. Purdy, Kathleen A. Grant

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    22 Scopus citations

    Abstract

    Previous studies showed that sensitivity to the ethanol-like discriminative stimulus effects of allopregnanolone and ethanol are enhanced during the luteal phase of the menstrual cycle when progesterone levels peak in monkeys trained to discriminate 1.0 g/kg ethanol. The present study further explored the influence of the menstrual cycle phase on the discriminative stimulus effects of ethanol, allopregnanolone, and midazolam. Female adult cynomolgus monkeys (Macaca fascicularis) were trained to discriminate 1.0 g/kg ethanol (n = 3) or 2.0 g/kg ethanol (n = 4) (20% w/v; IG) from water (IG). A cumulative dosing procedure was used to test discriminative stimulus effects of ethanol (0.5-2.5 g/kg; IG) and the ethanol-like discriminative stimulus effects of allopregnanolone (0.1-1.0 mg/kg; IV) or midazolam (1.0-17 mg/kg; IG) during the follicular vs. luteal phase of the menstrual cycle. In the 2.0-g/kg group, sensitivity to the ethanol- like effects of allopregnanolone was increased during the luteal vs. follicular phase in two of three monkeys. In contrast, average sensitivity to ethanol was not different in the luteal compared to the follicular phase in the 2.0-g/kg group. Finally, there was no difference in sensitivity to midazolam between the follicular and luteal phases in monkeys trained with either 2.0 g/kg or 1.0 g/kg ethanol. Overall, the ethanol-like discriminative stimulus effects of midazolam are not sensitive to the menstrual cycle phase. In addition, there was less influence of the menstrual cycle phase on allopregnanolone and ethanol sensitivity in a 2.0-g/kg compared to a 1.0-g/kg ethanol training dose. Copyright (C) 1999 Elsevier Science Inc.

    Original languageEnglish (US)
    Pages (from-to)379-383
    Number of pages5
    JournalPharmacology Biochemistry and Behavior
    Volume64
    Issue number2
    DOIs
    StatePublished - Oct 1 1999

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    Keywords

    • 3α-Hydroxy-5α-pregnan-20-one
    • Allopregnanolone
    • Cynomolgus monkeys
    • Drug discrimination
    • Ethanol
    • Menstrual cycle
    • Midazolam
    • Progesterone

    ASJC Scopus subject areas

    • Biochemistry
    • Toxicology
    • Pharmacology
    • Clinical Biochemistry
    • Biological Psychiatry
    • Behavioral Neuroscience

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