Investigating levodopa-induced dyskinesias in the Parkinsonian primate

Research into the cause of dyskinesias arising from levodopa treatment has been vexingly limited, partly due to the lack of an inexpensive and widely available animal model. Rodents do not develop levodopa-induced dyskinesias in a clinically recognizable form. However, nonhuman primates with 1-methy l-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism readily d evelop levodopa-induced dyskinesias that are virtually indistinguishable fr om those seen in patients with Parkinson's disease. We have developed and v alidated a five-point Global Primate Dyskinesia Rating Scale to accurately measure these dyskinesias. Monkeys with MPTP-induced parkinsonism were then investigated to evaluate the relationship between dyskinesias, parkinsonis m and severity of the nigrostriatal lesion. All parkinsonian animals were r esponsive to levodopa, and developed dyskinesias within 2-3 days of levodop a administration. Monkeys treated with only a single injection of MPTP also developed dyskinesias, even though they were not parkinsonian. It would ap pear that there is a different threshold of striatal dopamine depletion for parkinsonism and dyskinesias in the monkey. Finally, three hypotheses, put forward to explain the genesis of dyskinesias, are reviewed, and various e xperimental approaches suggested for each.