Decreased expression of l-dopa-induced dyskinesia by switching to ropinirole in MPTP-treated common marmosets.

Current concepts suggest that pulsatile stimulation of dopamine receptors following L-dopa administration leads to priming for dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-treated primates, while continuous dopaminergic stimulation with long-acting dopamine agonists does not. We investigated whether L-dopa-induced dyskinesia is reduced by switching to a dopamine agonist. MPTP-treated marmosets received chronic treatment with L-dopa or ropinirole in doses producing equivalent motor activity and reversal of motor deficits. Administration of L-dopa led to the rapid onset of moderate to severe dyskinesia, whereas ropinirole produced only mild dyskinesia. Animals initially treated with L-dopa were switched to an equivalent dose of ropinirole and those treated with ropinirole were switched to an equivalent dose of L-dopa for 56 days. L-dopa-primed animals that were switched to ropinirole showed a trend towards a reduction of dyskinesia intensity, whereas animals initially treated with ropinirole and switched to L-dopa showed a trend toward increased dyskinesia intensity. A subsequent, acute L-dopa challenge reversed motor deficits and induced intense dyskinesia in both groups. This suggests that L-dopa leads to the priming and expression of dyskinesia, but that expression is not maintained when switching to a long-acting dopamine agonist. In contrast, dopamine agonists may prime for dyskinesia, but do not lead to its full expression.