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Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson's disease.
Mov Disord. 2002 Nov; 17(6):1180-7.MD

Abstract

Long-term treatment with levodopa in Parkinson's disease results in the development of motor fluctuations, including reduced duration of antiparkinsonian action and involuntary movements, i.e., levodopa-induced dyskinesia. Cannabinoid receptors are concentrated in the basal ganglia, and stimulation of cannabinoid receptors can increase gamma-aminobutyric acid transmission in the lateral segment of globus pallidus and reduce glutamate release in the striatum. We thus tested the hypothesis that the cannabinoid receptor agonist nabilone (0.01, 0.03, and 0.10 mg/kg) would alleviate levodopa-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) -lesioned marmoset model of Parkinson's disease. Coadministration of nabilone (0.1 mg/kg) with levodopa was associated with significantly less total dyskinesia (dyskinesia score, 12; range, 6-17; primate dyskinesia rating scale) than levodopa alone (22; range, 14-23; P < 0.05). This effect was more marked during the onset period (0-20 minutes post levodopa). There was no reduction in the antiparkinsonian action of levodopa. Furthermore, the intermediate dose of nabilone used (0.03 mg/kg) increased the duration of antiparkinsonian action of levodopa by 76%. Thus, cannabinoid receptor agonists may be useful in the treatment of motor complications in Parkinson's disease.

Authors+Show Affiliations

Manchester Movement Disorder Laboratory, Division of Neuroscience, School of Biological Sciences, University of Manchester, Oxford Road, Manchester, United Kingdom. shfox@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12465055

Citation

Fox, Susan H., et al. "Stimulation of Cannabinoid Receptors Reduces Levodopa-induced Dyskinesia in the MPTP-lesioned Nonhuman Primate Model of Parkinson's Disease." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 17, no. 6, 2002, pp. 1180-7.
Fox SH, Henry B, Hill M, et al. Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson's disease. Mov Disord. 2002;17(6):1180-7.
Fox, S. H., Henry, B., Hill, M., Crossman, A., & Brotchie, J. (2002). Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson's disease. Movement Disorders : Official Journal of the Movement Disorder Society, 17(6), 1180-7.
Fox SH, et al. Stimulation of Cannabinoid Receptors Reduces Levodopa-induced Dyskinesia in the MPTP-lesioned Nonhuman Primate Model of Parkinson's Disease. Mov Disord. 2002;17(6):1180-7. PubMed PMID: 12465055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson's disease. AU - Fox,Susan H, AU - Henry,Brian, AU - Hill,Michael, AU - Crossman,Alan, AU - Brotchie,Jonathan, PY - 2002/12/5/pubmed PY - 2003/3/26/medline PY - 2002/12/5/entrez SP - 1180 EP - 7 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 17 IS - 6 N2 - Long-term treatment with levodopa in Parkinson's disease results in the development of motor fluctuations, including reduced duration of antiparkinsonian action and involuntary movements, i.e., levodopa-induced dyskinesia. Cannabinoid receptors are concentrated in the basal ganglia, and stimulation of cannabinoid receptors can increase gamma-aminobutyric acid transmission in the lateral segment of globus pallidus and reduce glutamate release in the striatum. We thus tested the hypothesis that the cannabinoid receptor agonist nabilone (0.01, 0.03, and 0.10 mg/kg) would alleviate levodopa-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) -lesioned marmoset model of Parkinson's disease. Coadministration of nabilone (0.1 mg/kg) with levodopa was associated with significantly less total dyskinesia (dyskinesia score, 12; range, 6-17; primate dyskinesia rating scale) than levodopa alone (22; range, 14-23; P < 0.05). This effect was more marked during the onset period (0-20 minutes post levodopa). There was no reduction in the antiparkinsonian action of levodopa. Furthermore, the intermediate dose of nabilone used (0.03 mg/kg) increased the duration of antiparkinsonian action of levodopa by 76%. Thus, cannabinoid receptor agonists may be useful in the treatment of motor complications in Parkinson's disease. SN - 0885-3185 UR - https://www.unboundmedicine.com/medline/citation/12465055/Stimulation_of_cannabinoid_receptors_reduces_levodopa_induced_dyskinesia_in_the_MPTP_lesioned_nonhuman_primate_model_of_Parkinson's_disease_ L2 - https://doi.org/10.1002/mds.10289 DB - PRIME DP - Unbound Medicine ER -