Comparison of the behavioral effects of bretazenil and flumazenil in triazolam-dependent and non-dependent baboons

Behavioral effects of the benzodiazepine receptor partial agonist bretazenil were compared with those of the benzodiazepine receptor antagonist flumazenil under conditions in which three baboons received continuous intragastric (i.g.) infusion of vehicle and then continuous i.g. infusion of triazolam (1.0 mg/kg/day). In each condition, acute doses of flumazenil (0.01-3.2 mg/kg) and bretazenil (0.01-10.0 mg/kg) were administered every 2 weeks (beginning after 30 days of treatment in the triazolam-dependent condition). Food pellets were available during daily 20-h sessions. Following test injections, 60-min behavioral observations were conducted followed by a fine motor assessment. During chronic vehicle administration, neither drug produced changes in observed behaviors. Bretazenil increased pellets earned and time to complete the fine-motor task (10.0 mg/kg dose). During chronic triazolam dosing, both bretazenil and flumazenil precipitated benzodiazepine withdrawal syndromes, characterized by vomiting, tremors/jerks, and a decrease in pellets earned. Thus, bretazenil can function as an antagonist under conditions of benzodiazepine physical dependence.