EFFECT OF CLONIDINE ON THE SCHEDULE-CONTROLLED PERFORMANCE ACTION OF TWO BENZODIAZEPINE RECEPTOR AGONISTS

Effect of clonidine, a presynaptic adrenoceptor agonist, on the schedule-controlled performance action of two benzodiazepine receptor agonists was assessed in rats in a fixed-ratio (FR6) procedure. Diazepam (0.03～1.0 mg/kg), an agonist of both type Ⅰ and Ⅱ benzodiazepine receptors, decreased the FR performance in a dose-dependent manner. Clonidine (10μg/kg) significantly potentiated the action of diazepam when the dose of diazepam was increased to 0.1 mg/kg. However, clonidine did not show any potentiating effect on the mild depressive action of CL 218, 872, a special agonist of type Ⅰ benzodiazepine receptor until its dose was increased to 10 mg/kg. The Potentiating effect of clonidine on the depressive action of diazepam was significantly antagonized by yohimbine. Bicueulline (3.0 mg/kg) significantly antagonized the depressive action of diazepam (1.0 mg/kg). Our results suggest that the depressive action of benzodiazepines on the function of central noradrenaline system may be one of the benzodiazepine sedative mechanisms, which may be related to the type Ⅱ benzodiazepine receptors.