Stimulation of cannabinoid receptors reduces levodopa-induced dyskinesia in the MPTP-lesioned nonhuman primate model of Parkinson's disease

Authors

  • Susan H. Fox MRCP, PhD,

    Corresponding author
    1. Manchester Movement Disorder Laboratory, Division of Neuroscience, School of Biological Sciences, University of Manchester, Oxford Road, Manchester, United Kingdom
    Current affiliation:
    1. Walton Centre for Neurology and Neurosurgery, Liverpool, United Kingdom
    • Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazakerley, Liverpool, L9 7LJ, United Kingdom
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  • Brian Henry PhD,

    1. Manchester Movement Disorder Laboratory, Division of Neuroscience, School of Biological Sciences, University of Manchester, Oxford Road, Manchester, United Kingdom
    Current affiliation:
    1. Organon Laboratories Limited, Lanarkshire, Scotland, ML1 5SH, United Kingdom
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  • Michael Hill PhD,

    1. Motac Neuroscience Ltd., Manchester Science Park, Manchester, United Kingdom
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  • Alan Crossman DSc,

    1. Motac Neuroscience Ltd., Manchester Science Park, Manchester, United Kingdom
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  • Jonathan Brotchie PhD

    1. Motac Neuroscience Ltd., Manchester Science Park, Manchester, United Kingdom
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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 γ-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. © 2002 Movement Disorder Society

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