Functional interaction between dopamine D1 and D2 receptors in 'MPTP' monkeys.

Abstract

We have studied the motor response induced by independent administration of 4 different doses of a dopamine D2 [(+)-PHNO] and a dopamine D1 (CY 208-243) receptor agonist in 5 MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkeys. Both drugs had similar antiparkinsonian effects and both elicited choreic dyskinesias. Simultaneous administration of (+)-PHNO [(+)-4-propyl-9-hydroxynaphthoxazine] and CY 208-243 [(-)4,6,6a,7,8,12b-hexahydro-7-methylindolo[4,3a-b]phenan thyxidine] did not result in modification of the dose-response curve induced by each dopamine receptor agonist given alone. Pretreatment with the dopamine D1 receptor antagonist SCH 23390 (0.8 mg/kg) and the dopamine D2 receptor antagonist sulpiride (60 mg/kg) reduced the magnitude and the duration of the motor response induced by (+)-PHNO and CY 208-243, respectively, but did not modify the intensity and characteristics of choreic dyskinesias. These results demonstrate that the motor effects and the dyskinesias cannot be dissociated by selective dopamine D1 and D2 receptor stimulation. It appears that stimulation of dopamine D1 and D2 receptors by endogenous dopamine is required to obtain the full motor response induced by selective dopamine receptor agonists as demonstrated by the reduction of the motor improvement found after pretreatment with SCH 23390 and sulpiride.