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Nicotine reduces levodopa-induced dyskinesias in lesioned monkeys.
Ann Neurol. 2007 Dec; 62(6):588-96.AN

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.

Authors+Show Affiliations

The Parkinson's Institute, Sunnyvale, CA 94089, USA. mquik@parkinsonsinstitute.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17960553

Citation

Quik, Maryka, et al. "Nicotine Reduces Levodopa-induced Dyskinesias in Lesioned Monkeys." Annals of Neurology, vol. 62, no. 6, 2007, pp. 588-96.
Quik M, Cox H, Parameswaran N, et al. Nicotine reduces levodopa-induced dyskinesias in lesioned monkeys. Ann Neurol. 2007;62(6):588-96.
Quik, M., Cox, H., Parameswaran, N., O'Leary, K., Langston, J. W., & Di Monte, D. (2007). Nicotine reduces levodopa-induced dyskinesias in lesioned monkeys. Annals of Neurology, 62(6), 588-96.
Quik M, et al. Nicotine Reduces Levodopa-induced Dyskinesias in Lesioned Monkeys. Ann Neurol. 2007;62(6):588-96. PubMed PMID: 17960553.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nicotine reduces levodopa-induced dyskinesias in lesioned monkeys. AU - Quik,Maryka, AU - Cox,Heather, AU - Parameswaran,Neeraja, AU - O'Leary,Kathryn, AU - Langston,J William, AU - Di Monte,Donato, PY - 2007/10/26/pubmed PY - 2008/1/23/medline PY - 2007/10/26/entrez SP - 588 EP - 96 JF - Annals of neurology JO - Ann Neurol VL - 62 IS - 6 N2 - 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. SN - 1531-8249 UR - https://www.unboundmedicine.com/medline/citation/17960553/Nicotine_reduces_levodopa_induced_dyskinesias_in_lesioned_monkeys_ L2 - https://doi.org/10.1002/ana.21203 DB - PRIME DP - Unbound Medicine ER -