Beginning-of-dose and rebound worsening in MPTP-treated common marmosets treated with levodopa.

A wide range of motor fluctuations develop in Parkinson's disease (PD) patients after prolonged levodopa (L-dopa) treatment, but few experimental models exist in which these can be investigated. We report on motor fluctuations occurring in MPTP-treated common marmosets (Callithrix jacchus) treated repeatedly with L-dopa. All animals showed an improvement in motor function in response to L-dopa, and rapidly developed peak-dose dyskinesia. During the period of L-dopa action, brief periods of immobility were occasionally observed. After acute L-dopa challenge, animals exhibited a worsening of motor function before improvement, and after the beneficial response to L-dopa declined, motor performance showed rebound worsening to below-baseline values. Before L-dopa challenge and during wearing-off and rebound worsening, leg dystonias were observed. Although these findings cannot necessarily be generalized to all MPTP-treated nonhuman primates, they demonstrate that MPTP-treated marmosets show a range of different motor fluctuations analogous to those seen in PD patients chronically treated with L-dopa. Therefore, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates can provide a model in which the pathophysiology of treatment complications can be investigated.