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

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Abstract
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

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