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

Abstract

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.

• Authors: S Boyce, N M Rupniak, M J Steventon, S D Iversen
• Journal: Clinical neuropharmacology (Clin Neuropharmacol) Vol. 13 Issue 5 Pg. 448-58 (Oct 1990) ISSN: 0362-5664 [Print] United States
• PMID: 2272024 (Publication Type: Journal Article)

Chemical References

• Levodopa

Topics

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