L-dopa dose and the duration and severity of dyskinesia in primed MPTP-treated primates

Abstract

Most patients with Parkinson's disease (PD) develop dyskinesia and other motor complications after prolonged L-dopa use. We now report on the relationship between L-dopa dose and the duration and severity of dyskinesia in L-dopa-primed MPTP-treated primates with marked nigral degeneration mimicking late stage PD. With increasing doses of L-dopa, locomotor activity increased and motor disability declined. The duration of dyskinesia following L-dopa administration increased dose-dependently, and showed a linear correlation with total locomotor activity. In addition, the time-course of dyskinesia paralleled closely that of locomotor activity in a dose-dependent manner. In contrast, severity of dyskinesia showed a non-linear correlation with total locomotor activity, low doses of L-dopa eliciting severe dyskinesia for short periods of time. The threshold for dyskinesia induction and the antiparkinsonian effects of L-dopa appear very similar in primed MPTP primates mimicking late stage PD. Reducing individual doses of L-dopa to avoid severe dyskinesia can markedly compromise the antiparkinsonian response. Our results extend the relevance of the dyskinetic MPTP-treated primate in studying the genesis of involuntary movements occurring in L-dopa treated patients with PD.