FUNCTIONAL INTERACTION BETWEEN DOPAMINE D-1 AND D-2 RECEPTORS IN MPTPMONKEYS

We have studied the motor response induced by independent administrati on of 4 different doses of a dopamine D-2 [(+)-PHNO] and a dopamine D- 1 (CY 208-243) receptor agonist in 5 MPTP (1-methyl-4-phenyl-1,2,3,6-t etrahydropyridine) monkeys. Both drugs had similar antiparkinsonian ef fects and both elicited choreic dyskinesias. Simultaneous administrati on of (+)-PHNO [(+)-4-propyl-9-hydroxynaphthoxazine] and CY 208-243 [( -)4,6,6a,7,8,12b-hexahydro-7-methylindolo phenanthyxidine] did not res ult in modification of the dose-response curve induced by each dopamin e receptor agonist given alone. Pretreatment with the dopamine D-1 rec eptor antagonist SCH 23390 (0.8 mg/kg) and the dopamine D-2 receptor a ntagonist 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 dysk inesias. These results demonstrate that the motor effects and the dysk inesias cannot be dissociated by selective dopamine D-1 and D-2 recept or stimulation. It appears that stimulation of dopamine D-1 and D-2 re ceptors by endogenous dopamine is required to obtain the full motor re sponse induced by selective dopamine receptor agonists as demonstrated by the reduction of the motor improvement found after pretreatment wi th SCH 23390 and sulpiride.