Induction of chorea and dystonia in parkinsonian primates.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in primates induced a parkinsonian syndrome that could be reversed by levodopa treatment. Animals quickly developed an apparent restlessness ("akathisia") of the lower limbs after as little as five doses. After 4-10 weeks of regular levodopa therapy, animals developed "peak dose" choreiform movements in the lower limbs that spread, with time, to involve the upper limbs and orofacial musculature. With further treatment (5-21 months), animals developed "peak dose" dystonia that variably involved the limbs and orofacial musculature. These conditions represent novel models of levodopa-induced chorea and dystonia in humans. They depend on the same underlying neuropathology and treatment regimen as their human counterparts. It is to be anticipated that these models of dyskinesia will be useful in determining the mechanisms underlying chorea and dystonia in humans and are ideally suited for experimental evaluation of new treatment strategies.