Discriminative stimulus effects of the endogenous neuroactive steroid pregnanolone.

Naive male Sprague-Dawley rats were trained to discriminate the endogenous neuroactive steroid pregnanolone (5.6 mg/kg) from saline. Three positive modulators of the GABA(A) receptor complex substituted for pregnanolone: the neuroactive steroid allopregnanolone (1.0-10.0 mg/kg), the barbiturate pentobarbital (3.0-17.0 mg/kg), and the benzodiazepine diazepam (0.3-3.0 mg/kg). In contrast, buspirone, a 5-HT1A-mediated anxiolytic, failed to substitute up to rate-suppressing doses (1.0-5.6 mg/kg). The present experiment demonstrated the ability of an endogenous neuroactive steroid to function as a discriminative stimulus. Moreover, these results suggest that the discriminative stimulus effects of pregnanolone are mediated via positive modulation of GABA(A) receptors.