Discriminative stimulus effects of ethanol and 3 alpha-hydroxy-5 alpha-pregnan-20-one in relation to menstrual cycle phase in cynomolgus monkeys (Macaca fascicularis)

The present study was designed to characterize the discriminative stimulus effects of ethanol and the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) in nonhuman primates as a function of menstrual cycle phase. Female cynomolgus monkeys (Macaca fascicularis) were trained in a two-lever procedure to discriminate 1.0 g/kg ethanol (IG, 30 min pretreatment) from water using food reinforcement. A cumulative dosing procedure was used to assess changes in the potency of ethanol and an endogenous anxiolytic steroid in the follicular versus the luteal phase of the menstrual cycle. Plasma progesterone and allopregnanolone levels were determined within 24 h of testing to verify phase of menstrual cycle. The monkeys were more sensitive to the dis criminative stimulus effects of ethanol and the ethanol-like effects of the endogenous neuroactive steroid allopregnanolone during the luteal phase of the menstrual cycle. These findings suggest that changes in the endogenous levels of ovarian-derived progesterone and allopregnanolone alter sensitivity to the discriminative stimulus effects of ethanol.