Decreased expression of l-dopa-induced dyskinesia by switching to ropinirole in MPTP-treated common marmosets.
Current concepts suggest that pulsatile stimulation of dopamine receptors following L-dopa administration leads to priming for dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-treated primates, while continuous dopaminergic stimulation with long-acting dopamine agonists does not. We investigated whether L-dopa-induced dyskinesia is reduced by switching to a dopamine agonist. MPTP-treated marmosets received chronic treatment with L-dopa or ropinirole in doses producing equivalent motor activity and reversal of motor deficits. Administration of L-dopa led to the rapid onset of moderate to severe dyskinesia, whereas ropinirole produced only mild dyskinesia. Animals initially treated with L-dopa were switched to an equivalent dose of ropinirole and those treated with ropinirole were switched to an equivalent dose of L-dopa for 56 days. L-dopa-primed animals that were switched to ropinirole showed a trend towards a reduction of dyskinesia intensity, whereas animals initially treated with ropinirole and switched to L-dopa showed a trend toward increased dyskinesia intensity. A subsequent, acute L-dopa challenge reversed motor deficits and induced intense dyskinesia in both groups. This suggests that L-dopa leads to the priming and expression of dyskinesia, but that expression is not maintained when switching to a long-acting dopamine agonist. In contrast, dopamine agonists may prime for dyskinesia, but do not lead to its full expression.
Jackson
Michael J
MJ
Neurodegenerative Diseases Research Centre, School of Health and Biomedical Sciences, King's College, London SE1 1UL, UK.
Smith
Lance A
LA
Al-Barghouthy
Ghassan
G
Rose
Sarah
S
Jenner
Peter
P
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002144:Callithrix; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects
D015259:Dopamine Agents; D018491:Dopamine Agonists; D007211:Indoles; C046649:ropinirole; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine