Selective D2 receptor stimulation induces dyskinesia in parkinsonian monkeys

Stimulation of D1 striatal receptors has been proposed as the main mechanism mediating levodopa-induced dyskinesia in Parkinson's disease. We used (+)-PHNO, a selective D2 agonist, as the only treatment in 6 cynomolgus monkeys made parkinsonian by repeated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. All animals developed choreic dyskinesia after a mean treatment period of 12.8 days (range, 1-29). Administration of the D1 antagonist SCH-23390 1 hour before administration of (+)-PHNO did not change the dyskinesia. These results indicate that drug-induced dyskinesia in a primate model of Parkinson's disease is not solely induced by D1 receptor activation.