title: Nicotine reduces levodopa-induced dyskinesias in lesioned monkeys.
abstract: OBJECTIVE
  Levodopa, the gold standard for Parkinson's disease treatment, is associated with debilitating abnormal involuntary movements or dyskinesias, for which few treatments are currently available. Studies have implicated numerous neurotransmitters in the development of levodopa-induced dyskinesias. However, the cholinergic system has received little attention despite an extensive overlap between dopaminergic terminals and cholinergic interneurons in the striatum and the well-known ability of nicotine to stimulate striatal dopamine release. Our objective, therefore, was to determine whether nicotine treatment reduced levodopa-induced dyskinesias.
  
  
  METHODS
  The effect of nicotine (provided in the drinking water) was determined on dyskinesias induced by levodopa (5 mg/kg twice daily by oral gavage) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys.
  
  
  RESULTS
  Nicotine pretreatment reduced peak and total levodopa-induced dyskinesias in levodopa-naive monkeys over an 8-week period, with a decrease in total dyskinesias of about 50%. A crossover study was then done in which levodopa-treated monkeys originally receiving vehicle were administered nicotine, whereas the levodopa-treated animals initially receiving nicotine were placed on vehicle. Nicotine treatment to levodopa-primed monkeys led to an approximately 35% reduction in total dyskinesias that lasted for at least 8 weeks, at which time the study was ended. In contrast, a significant increase in levodopa-induced dyskinesias was observed in the group of animals that had previously received nicotine and were then switched to vehicle. Nicotine treatment did not appear to affect the antiparkinsonian action of levodopa.
  
  
  CONCLUSIONS
  These data suggest that nicotine or selective nicotinic agonists may represent a useful treatment strategy to reduce levodopa-induced dyskinesias.
authors.affiliation: The Parkinson's Institute, Sunnyvale, CA 94089, USA. mquik@parkinsonsinstitute.org
authors.forename: Maryka
authors.initials: M
authors.lastname: Quik
authors.forename: Heather
authors.initials: H
authors.lastname: Cox
authors.forename: Neeraja
authors.initials: N
authors.lastname: Parameswaran
authors.forename: Kathryn
authors.initials: K
authors.lastname: O'Leary
authors.forename: J William
authors.initials: JW
authors.lastname: Langston
authors.forename: Donato
authors.initials: D
authors.lastname: Di Monte
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002940:Circadian Rhythm; D004409:Dyskinesia, Drug-Induced / Q000473:pathology / Q000503:physiopathology*; D007980:Levodopa / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000503:physiopathology; D012453:Saimiri; D013378:Substantia Nigra / Q000473:pathology; D013997:Time Factors
chemical_list: D018722:Nicotinic Agonists; D007980:Levodopa; D009538:Nicotine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine