Yohimbine's anxiogenic action: evidence for noradrenergic and dopaminergic sites

Yohimbine (2.5 or 4 mg/kg) reduced the percentage of open arm entries and the percentage of time spent on the open arms displayed by rats on an elevated plus-maze indicating anxiogenic activity. These effects were reversed by the alpha 2-adrenoceptor agonist clonidine (0.01 mg/kg) and by the dopamine receptor agonist apomorphine (0.57 mg/kg). The following failed to reverse the effects of yohimbine: the selective alpha 2-adrenoceptor agonists, guanfacine (0.25 and 1 mg/kg), B-HT920 (0.025 and 0.1 mg/kg), B-HT933 (1 and 10 mg/kg); the beta-blocker propranolol (2.5 and 10 mg/kg); the alpha 1-adrenoceptor agonist phenylephrine; the D1 agonist SK&F 38393 (5 and 10 mg/kg) and the D2 agonist LY 171555 (0.5 and 1 mg/kg). Therefore, it is unlikely that activity at only the alpha 1, alpha 2, beta, D1 or D2 sites can entirely account for the anxiogenic actions of yohimbine in the elevated plus-maze. Evidence that clonidine affects the dopaminergic system and that apomorphine affects the noradrenergic system suggest that yohimbine may produce its anxiogenic response by activity on both the noradrenergic and dopaminergic systems.