L-dopa dose and the duration and severity of dyskinesia in primed MPTP-treated primates.
Most patients with Parkinson's disease (PD) develop dyskinesia and other motor complications after prolonged L-dopa use. We now report on the relationship between L-dopa dose and the duration and severity of dyskinesia in L-dopa-primed MPTP-treated primates with marked nigral degeneration mimicking late stage PD. With increasing doses of L-dopa, locomotor activity increased and motor disability declined. The duration of dyskinesia following L-dopa administration increased dose-dependently, and showed a linear correlation with total locomotor activity. In addition, the time-course of dyskinesia paralleled closely that of locomotor activity in a dose-dependent manner. In contrast, severity of dyskinesia showed a non-linear correlation with total locomotor activity, low doses of L-dopa eliciting severe dyskinesia for short periods of time. The threshold for dyskinesia induction and the antiparkinsonian effects of L-dopa appear very similar in primed MPTP primates mimicking late stage PD. Reducing individual doses of L-dopa to avoid severe dyskinesia can markedly compromise the antiparkinsonian response. Our results extend the relevance of the dyskinetic MPTP-treated primate in studying the genesis of involuntary movements occurring in L-dopa treated patients with PD.
Kuoppamäki
M
M
Neurodegenerative Diseases Research Centre, King's College, London, U.K. mikkuo@utu.fi
Al-Barghouthy
G
G
Jackson
M J
MJ
Smith
L A
LA
Quinn
N
N
Jenner
P
P
D000818:Animals; D002144:Callithrix; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005260:Female; D007980:Levodopa / Q000008:administration & dosage* / Q000633:toxicity; D020267:MPTP Poisoning / Q000503:physiopathology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D012720:Severity of Illness Index
D007980:Levodopa