Differential effects of D 1 and D 2 agonists in MPTP‐treated primates

Abstract

Administration of the indirect agonist L-dopa, the nonselective direct agonist apomorphine, or the selective D₂ agonist (+)-PHNO, reversed parkinsonism and induced locomotor activation in MPTP-treated squirrel monkeys. In contrast, administration of the selective partial D₁ agonist SKF38393 did not induce locomotor activity, but rather decreased activity. Choreiform movements were observed only following treatment with L-dopa. Coadministration of the D₁ antagonist SCH23390 prevented L-dopa-induced chorea at the time of peak effect. However, a rebound exaggeration of chorea was observed following SCH23390 at the time when chorea induced by L-dopa alone would normally be subsiding. Unlike chorea, dystonia could be induced by treatment with either L-dopa or (+)-PHNO. Administration of apomorphine failed to significantly induce dystonia, although a small increase was observed with the highest dose. Treatment with SKF38393 actually decreased dystonia. Our findings clearly indicate that D₂ receptor stimulation appears essential for antiparkinsonian activity, and also implicate D₂ receptors in the genesis of dystonia, but not chorea. D₁ receptor stimulation appears to be involved in the genesis of chorea and possibly also dystonia.