Nigrostriatal damage is required for induction of dyskinesias by L-DOPA in squirrel monkeys.
We examined the ability of L-DOPA to induce dyskinesias in MPTP-treated and normal squirrel monkeys to establish whether the underlying neuropathology associated with parkinsonism is an absolute requirement or merely promotes the development of drug-induced dyskinesias. Administration of L-DOPA (5-40 mg/kg p.o., following a 60 min pretreatment with carbidopa 2.5-20 mg/kg p.o.) induced a range of dopamine-mediated behaviours including locomotor activity, stereotyped scratching, and climbing in both lesioned and nonlesioned animals. However, the dose-response curves showed a marked (three- to fourfold) shift to the left in lesioned animals, indicating behavioural supersensitivity. In contrast, L-DOPA-induced dyskinesias were only observed in MPTP-treated monkeys. Doses required for induction of dyskinesias were lower than those required to induce climbing. These findings provide further evidence that nigrostriatal damage is essential for the genesis of L-DOPA-induced dyskinesias.
Boyce
S
S
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Essex, U.K.
Rupniak
N M
NM
Steventon
M J
MJ
Iversen
S D
SD
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004409:Dyskinesia, Drug-Induced / Q000473:pathology*; D007980:Levodopa / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D012453:Saimiri; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology*
D007980:Levodopa