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

Previous studies showed that sensitivity to the ethanol-like discriminative stimulus effects of allopregnanolone and ethanol are enhanced during the l uteal phase of the menstrual cycle when progesterone levels peak in monkeys trained to discriminate 1.0 g/kg ethanol. The present study further explor ed the influence of the menstrual cycle phase on the discriminative stimulu s effects of ethanol, allopregnanolone, and midazolam. Female adult cynomol gus monkeys (Macaca fascicularis) were trained to discriminate 1.0 g/kg eth anol (n = 3) or 2.0 g/kg ethanol (n = 4) (20% w/v; IG) from water (IG). A c umulative 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 allopregnanolo ne was increased during the luteal vs. follicular phase in two of three mon keys. 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, the re 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 in fluence of the menstrual cycle phase on allopregnanolone and ethanol sensit ivity in a 2.0-g/kg compared to a 1.0-g/kg ethanol training dose. (C) 1999 Elsevier Science Inc.