Continuous rotigotine administration reduces dyskinesia resulting from pulsatile treatment with rotigotine or l-DOPA in MPTP-treated common marmosets

Abstract

We previously showed that continuous infusion of rotigotine resulted in less dyskinesia than repeated pulsatile rotigotine administration or repeated oral administration of l-DOPA in MPTP-treated marmosets. Now we investigate whether continuous rotigotine delivery modifies established dyskinesia induced by prior exposure to repeated pulsatile administration of l-DOPA or rotigotine in MPTP-treated common marmosets. Repeated oral administration of l-DOPA or subcutaneous bolus administration of rotigotine over 28 days improved motor deficits but resulted in the onset of dyskinesia of moderate intensity. When these animals were switched to a 28-day continuous infusion of rotigotine, the reversal of motor disability was maintained. In those animals initially treated with l-DOPA, there was a small reduction in dyskinesia intensity but a significant reduction in the duration of dyskinesia. However, in animals initially treated with repeated bolus administration of rotigotine, dyskinesia intensity was significantly reduced. Initial treatment with a continuous infusion of rotigotine for 28 days reversed motor disability and resulted in a low incidence of dyskinesia. On switching to repeated oral administration of l-DOPA, the improvement in motor disability was maintained but the propensity of l-DOPA to provoke dyskinesia was not affected. In addition, while the continuous delivery of rotigotine prevented the expression of dyskinesia, the previously demonstrated ability of dopamine agonists to prime for dyskinesia could not be avoided. These data suggest that dyskinesia induced by pulsatile drug treatment may be improved by switching to continuous rotigotine delivery. In addition, while continuous delivery of rotigotine may prime for dyskinesia, it does not lead to its expression.