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. INTERPRETATION: These data suggest that nicotine or selective nicotinic agonists may represent a useful treatment strategy to reduce levodopa-induced dyskinesias.
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In parkinsonian monkeys, nicotine delivered through drinking water cut L-DOPA-induced dyskinesias by roughly half.
“Nicotine administered via drinking water attenuated L-DOPA-in- duced dyskinesias by approximately 50% in parkinsonian monkeys (Quik et al., 2007).”
From Nicotinic receptor-mediated reduction in l-DOPA-induced dyskinesias may occur via desensitization (2010) · cites this paper as Quik et al., 2007
Intermittent nicotine exposure via drinking water effectively reduces AIMs in both rats and monkeys.
“In addition, our previous data demonstrate that intermittent exposure via drinking water also effectively reduces AIMs in both rats and monkeys (Quik et al., 2007;Bordia et al., 2008).”
From Nicotinic receptor-mediated reduction in l-DOPA-induced dyskinesias may occur via desensitization (2010) · cites this paper as Quik et al., 2007
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Nicotine and Parkinson's disease: implications for therapy
Quik, M., O'Leary, K., & Tanner, C. M. (2008) · Movement Disorders · doi:10.1002/mds.21900 · Cited by 154 · see citing works
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Self-citationNicotinic receptor-mediated reduction in l-DOPA-induced dyskinesias may occur via desensitization
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- Authors
- Quik, M., Cox, H., Parameswaran, N., O'Leary, K., Langston, J. W., & Di Monte, D.
- Affiliations
- Parkinson's Institute and Clinical Center (US)
- Corresponding author
- Quik, Maryka
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2007-10-24
- Volume
- 62
- Issue
- 6
- Pages
- 588-596
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2114682795
- Cited by
- 133
- References
- 50
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 11 · 2014: 11 · 2013: 15 · 2012: 13
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (NINDS 34886, NINDS 42091)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine, levodopa-induced dyskinesia, Parkinson's disease, MPTP lesion, cholinergic system, nicotinic agonists, striatum, dopamine release, antiparkinsonian effects, involuntary movements
- MeSH terms
- Animals, Circadian Rhythm, Dyskinesia, Drug-Induced, Levodopa, Nicotine, Saimiri, Substantia Nigra, Time Factors, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Nicotinic Agonists, Parkinsonian Disorders
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