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.
Vanover
K E
KE
Department of Pharmacology, CoCensys, Inc., Irvine, CA 92618, USA. kim@rat.ucsd.edu
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004193:Discrimination Learning; D004305:Dose-Response Relationship, Drug; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism
D011963:Receptors, GABA-A; D011280:Pregnanolone; D010424:Pentobarbital; D003975:Diazepam