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.