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.
Kuoppamäki
Mikko
M
Neurodegenerative Diseases Research Centre, King's College, London, United Kingdom.
Al-Barghouthy
Ghassan
G
Jackson
Michael
M
Smith
Lance
L
Zeng
Bai-Yun
BY
Quinn
Niall
N
Jenner
Peter
P
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002144:Callithrix; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005260:Female; D007980:Levodopa / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D009460:Neurologic Examination / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology*; D012008:Recurrence
D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine