Disruption of schedule-controlled behavior by Ro 15-1788 one day after acute treatment with benzodiazepines

Abstract

The behavioral effects of the benzodiazepine antagonist Ro 15-1788 were studied in squirrel monkeys after acute injections of benzodiazepines. Monkeys responded under a multiple schedule of food presentation with alternating fixed-interval (FI) and fixed-ratio (FR) components, Chlordiazepoxide (10 mg/kg) increased FI responding and had little effect on FR responding 1 h after it was administered; FI responding was still elevated during the session on the following day. When Ro 15-1788 (0.1-3 mg/kg) was administered 1 h after chlordiazepoxide, it antagonized the effects of chlordiazepoxide in a dose-related manner. When Ro 15-1788 was administered 1 day after chlordiazepoxide, however, doses of 1 or 3 mg/kg suppressed both FI and FR responding. Suppression of schedule-controlled responding was also observed when Ro 15-1788 (3 mg/kg) was administered 1 day after diazepam (3 or 5.6 mg/kg) or N-desmethyldiazepam (5.6 mg/kg). The results show that Ro 15-1788 can precipitate disruption of schedule-controlled behavior 1 day after acute treatment with benzodiazepines.