ETHANOL-LIKE DISCRIMINATIVE STIMULUS EFFECTS OF THE NEUROSTEROID 3-ALPHA-HYDROXY-5-ALPHA-PREGNAN-20-ONE IN FEMALE MACACA-FASCICULARIS MONKEYS

The present study was designed to characterize the discriminative stim ulus effects of ethanol and the neurosteroid 3 alpha-hydroxy-5 alpha-p regnan-20-one (allopregnanolone) in non-human primates. Female cynomol gus monkeys (Macaca fascicularis) were trained in a two-lever procedur e to discriminate 1.0 g/kg ethanol (IG, 30 min pretreatment) from wate r using food reinforcement. Consistent with previous results in a vari ety of species, pentobarbital (0.56-17 mg/kg, IG) resulted in a dose-d ependent substitution for the discriminative stimulus effects of ethan ol, with an average ED(50) value of 1.9 mg/kg. Administration of allop regnanolone (0.3-5.6 mg/kg, IV) also produced complete substitution fo r the discriminative stimulus effects of ethanol, with an ED(50) value of 1.0 mg/kg. Plasma allopregnanolone levels 35 min following the adm inistration of 3.0 mg/kg allopregnanolone ranged from 33 to 69 ng/ml. The ethanol-like discriminative stimulus effects of 1.0 mg/kg allopreg nanolone (IV) were present for 60 min, with a return to complete water -appropriate responding at 90 min post-treatment. The results indicate that the endogenous neuroactive steroid allopregnanolone produces sub jective effects in cynomolgus monkeys that are similar to ethanol. The se findings suggest that changes in the endogenous levels of allopregn anolone could alter sensitivity to the subjective effects of ethanol.