Intracranial self-stimulation distinguishes between two benzodiazepine antagonists.
Low doses of Ro 15-1788 and CGS 8216 were without effect on variable-interval self-stimulation, but completely abolished the enhancement of responding produced by chlordiazepoxide (5 mg/kg). Higher doses of Ro 15-1788, unlike other benzodiazepine receptor antagonists, produced an increase in response rates similar to that found after chlordiazepoxide. This result is consistent with its suggested action as a partial agonist. The combination of a high (benzodiazepine-like) dose of Ro 15-1788 with chlordiazepoxide produced a depression of responding similar to that seen with high doses of benzodiazepines. High doses of CGS 8216 produced a depression of self-stimulation, which was not reversed by chlordiazepoxide (5 mg/kg). Thus, the present procedure is able to distinguish contrasting behavioural effects of benzodiazepine antagonists.
D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000037:antagonists & inhibitors*; D004338:Drug Combinations; D005442:Flumazenil; D007026:Hypothalamic Area, Lateral / Q000187:drug effects*; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012653:Self Stimulation / Q000187:drug effects*
D001570:Benzodiazepinones; D004338:Drug Combinations; D011720:Pyrazoles; D005442:Flumazenil; D002707:Chlordiazepoxide; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one