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L-dopa dose and the duration and severity of dyskinesia in primed MPTP-treated primates

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Summary

Most patients with Parkinson’s disease (PD) develop dyskinesia and other motor complications after prolonged L-dopa use. We now report on the relationship between L-dopa dose and the duration and severity of dyskinesia in L-dopa-primed MPTP-treated primates with marked nigral degeneration mimicking late stage PD. With increasing doses of L-dopa, locomotor activity increased and motor disability declined. The duration of dyskinesia following L-dopa administration increased dose-dependently, and showed a linear correlation with total locomotor activity. In addition, the time-course of dyskinesia paralleled closely that of locomotor activity in a dose-dependent manner. In contrast, severity of dyskinesia showed a non-linear correlation with total locomotor activity, low doses of L-dopa eliciting severe dyskinesia for short periods of time. The threshold for dyskinesia induction and the antiparkinsonian effects of L-dopa appear very similar in primed MPTP primates mimicking late stage PD. Reducing individual doses of L-dopa to avoid severe dyskinesia can markedly compromise the antiparkinsonian response. Our results extend the relevance of the dyskinetic MPTP-treated primate in studying the genesis of involuntary movements occurring in L-dopa treated patients with PD.

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Authors and Affiliations

  1. Neurodegenerative Diseases Research Centre, King’s College, London, U.K.

    M. Kuoppamäki, G. Al-Barghouthy, M. J. Jackson, L. A. Smith & P. Jenner

  2. Department of Neurology, Turku University Hospital, Turku, Finland

    M. Kuoppamäki

  3. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, London, U.K.

    N. Quinn

Authors
  1. M. Kuoppamäki
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  2. G. Al-Barghouthy
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  3. M. J. Jackson
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  4. L. A. Smith
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  5. N. Quinn
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  6. P. Jenner
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Kuoppamäki, M., Al-Barghouthy, G., Jackson, M. et al. L-dopa dose and the duration and severity of dyskinesia in primed MPTP-treated primates. J Neural Transm 114, 1147–1153 (2007). https://doi.org/10.1007/s00702-007-0727-3

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  • DOI: https://doi.org/10.1007/s00702-007-0727-3

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