Effect of chronic treatment with (+)-PHNO, a D2 agonist in MPTP-treated monkeys.

A group of four drug naive Macaca fascicularis were rendered parkinsonian with the neurotoxin 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine and then treated chronically with (+)-PHNO, a potent D2 agonist. After several days, dyskinesia appeared in all animals. At this point, the daily dose of (+)-PHNO was replaced by a dose of the D1 agonist CY 208-243. The substitution by CY 208-243 reproduced the same dyskinesia observed with (+)-PHNO. The administration of the DA synthesis inhibitor AMPT (alpha-methyl-p-tyrosine methyl ester) blocked the dyskinetic and antiparkinsonian effect of (+)-PHNO, and those effects were reestablished by the addition of a subthreshold dose of CY 208-243. Our results show that a selective D2 agonist is capable of inducing dyskinesia and suggest some kind of cooperation between D1 and D2 receptors in the antiparkinsonian and dyskinetic effect produced by (+)-PHNO.