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. © 2002 Movement Disorder Society