Kl. Green et al., The influence of menstrual cycle phase on sensitivity to ethanol-like discriminative stimulus effects of GABA(A)-positive modulators, PHARM BIO B, 64(2), 1999, pp. 379-383
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.