POTENTIATION OF DOPAMINE-DEPENDENT LOCOMOTION BY CLONIDINE IN RESERPINE-TREATED MICE IS RESTRICTED TO D-2 AGONISTS

Mice treated with reserpine (5 mg/kg IP), 24 h beforehand, were completely akinetic. Fluent locomotion was reinstated with the D-1-selective agonist SKF 38393 (3-30 mg/kg IP), the D-2-selective agonist RU 24213 (0.5-5 mg/kg SC) and the mixed D-1/D-2 agonist apomorphine (0.025-0.5 mg/kg SC). Clonidine (0.03125-1 mg/kg IP) caused a dose-dependent sedation in dopamine-intact mice, but had no effect by itself on the locomotor activity of monoamine-depleted mice. In drug interaction experiments, clonidine did not modify the motor stimulant action of SKF 38393, but greatly enhanced the motor responses to RU 24213 and apomorphine. These results support the hypothesis that alpha-adrenoceptor agonists facilitate dopamine D-2 but not dopamine D-1 motor responding in the reserpine-treated mouse model of Parkinson's disease.