The use of flumazenil in prevention of Diazepam dependence in the rat

Abstract Rats were treated with diazepam (4 mg/kg per day) or its vehicle for 21 days. Twenty‐four hours after their last dose they were tested in the social interaction test of anxiety. Diazepam withdrawal significantly reduced the time spent in social interaction compared with controls, indicating an anxiogenic withdrawal response. The administration of a single dose of flumazenil (4 mg/kg) during chronic diazepam treatment, 7 or 14 days before testing, prevented the development of this withdrawal response. The clinical implications of these findings are discussed.