Nigrostriatal damage is required for induction of dyskinesias by L-DOPA in squirrel monkeys

Clin Neuropharmacol. 1990 Oct;13(5):448-58. doi: 10.1097/00002826-199010000-00006.


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.

MeSH terms

  • Animals
  • Corpus Striatum / drug effects
  • Corpus Striatum / pathology*
  • Dyskinesia, Drug-Induced / pathology*
  • Levodopa / toxicity*
  • Male
  • Motor Activity / drug effects
  • Saimiri
  • Substantia Nigra / drug effects
  • Substantia Nigra / pathology*


  • Levodopa