Nicotine reduces levodopa-induced dyskinesias in lesioned monkeys

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 dys...

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Bibliographic Details
Published in:Annals of neurology Vol. 62; no. 6; pp. 588 - 596
Main Authors: Quik, Maryka, Cox, Heather, Parameswaran, Neeraja, O'Leary, Kathryn, Langston, J. William, Di Monte, Donato
Format: Journal Article
Language:English
Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2007
Willey-Liss
Subjects:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Biological and medical sciences
Circadian Rhythm
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Drug toxicity and drugs side effects treatment
Dyskinesia, Drug-Induced - pathology
Dyskinesia, Drug-Induced - physiopathology
Levodopa - pharmacology
Medical sciences
Neurology
Nicotine - pharmacology
Nicotinic Agonists - pharmacology
Parkinsonian Disorders - physiopathology
Pharmacology. Drug treatments
Saimiri
Substantia Nigra - pathology
Time Factors
Toxicity: nervous system and muscle
Nervous system diseases
Monkey
Involuntary movement
Cerebral disorder
Vertebrata
Mammalia
Animal
Central nervous system disease
Primates
Levodopa
Neurological disorder
Extrapyramidal syndrome
Dyskinesia
Nicotine
ISSN:0364-5134, 1531-8249, 1531-8249
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Summary: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 (5mg/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. Interpretation These data suggest that nicotine or selective nicotinic agonists may represent a useful treatment strategy to reduce levodopa‐induced dyskinesias. Ann Neurol 2007
Bibliography:(NIH NINDS) - No. 42091; No. 34886
ark:/67375/WNG-Q7KP5R1T-T
ArticleID:ANA21203
istex:60434D3A8E9DFA0D6BFD825DCFC2A95648542A2D
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0364-5134
1531-8249
1531-8249
DOI:10.1002/ana.21203