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.