CHLORDIAZEPOXIDE, BUT NOT BRETAZENIL, PRODUCES ACUTE DEPENDENCE, AS EVIDENCED BY DISRUPTIONS IN SCHEDULE-CONTROLLED BEHAVIOR

The purpose of the present study was to determine whether the full benzodiazepine (BDZ) agonist chlordiazepoxide (CDAP) and the partial BDZ agonist bretazenil would produce acute dependence in rats, as evidenced by disruptions in fixed-interval responding during precipitated abstinence withdrawal. Doses of CDAP and bretazenil administered acutely were 10, 75, and 100 mg/kg; flumazenil (1-56 mg/kg) was administered 1, 2, 4, or 18 h later. Withdrawal, defined as a significant decrease in fixed-interval responding, was only seen when a high dose of flumazenil was administered 18 h after 100 mg/kg of CDAP. These results support those of others (5) who found that high (75-450 mg/kg) doses of CDAP were required to produce acute physical dependence. That bretazenil did not produce acute physical dependence supports the findings of others (20,23) who report that chronic administration of bretazenil does not result in physical dependence.