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 (Kathy) Grant

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 1999
Externally publishedYes

Fingerprint

Menstrual Cycle
gamma-Aminobutyric Acid
Modulators
Ethanol
Pregnanolone
Midazolam
Follicular Phase
Luteal Phase
Haplorhini
Macaca fascicularis
Corpus Luteum
Progesterone

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

The influence of menstrual cycle phase on sensitivity to ethanol-like discriminative stimulus effects of GABA(A)-positive modulators. / Green, Kristen L.; Azarov, Alexey V.; Szeliga, Kendall T.; Purdy, Robert H.; Grant, Kathleen (Kathy).

In: Pharmacology Biochemistry and Behavior, Vol. 64, No. 2, 10.1999, p. 379-383.

Research output: Contribution to journalArticle

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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.",
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