Effects of agonist and inverse agonist of central benzodiazepine receptors on discriminative yohimbine stimulation

The effects of agonist and inversc agonist of benzodiazepine receptors on aiscriminative yohimbine stimulation were assessed in rats trained using a two-lever yohimbine cue discrimination procedure. The yohimbine cue was antagonized by both clonidine (0.03-0.5 mg/kg ip) and diazepam (0.1-10.0 mg/kg ip) in a dose-dependcnt manner. Clonidine (30,60 ug/kg ip) significantly potentiated the deprcssive effects of diazepam on the yohimbine cue. Yohimbine cue was only partially gencralized to pentylenctetrazol (1-30 mg/kg ip) and DMCM (methyl-4-etnyl-6,7-dimetho-xy-(b-carboline-3-carboxylate, 0.1-0.7 mg/kg ip). However, DMCM (0.1 mg/kg ip) significantly potentiated the yohimbine cue, which was indicated by the significant shift of dose-effect curve of yohimbinc cue to the left. This potentiating effect of DMCM on the yohimbine cue was antagonized by both flumazepil (3.0 mg/kg ip). an antagonist of benzodiazepine receptors. and CL-21887l (3.0 mg/kg ip) an agorist of type I benzodiazepine receptors, respectively. Our results suggest that the noradrenergic system may be involved in both the anxiolytic efiect of benzodiozepinc rcceptor agonists and the axiogenic action of inverse benzodiazepine receptor agonists.