Levodopa gains psychostimulant-like properties after nigral dopaminergic loss

Authors

  • Michel Engeln MS,

    1. Institute of Neurodegenerative Diseases, UMR 5293, F-33000 Bordeaux, France, University of Bordeaux, Bordeaux, France
    2. Institute of Neurodegenerative Diseases, UMR 5293, F-33000 Bordeaux, France, National Center for Scientific Research, Bordeaux, France
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  • Stefania Fasano PhD,

    1. Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Research Institute, Milan, Italy
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  • Serge H. Ahmed PhD,

    1. Institute of Neurodegenerative Diseases, UMR 5293, F-33000 Bordeaux, France, University of Bordeaux, Bordeaux, France
    2. Institute of Neurodegenerative Diseases, UMR 5293, F-33000 Bordeaux, France, National Center for Scientific Research, Bordeaux, France
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  • Martine Cador PhD,

    1. Aquitaine Institute of Cognitive and Integrative Neurosciences, University of Bordeaux, Bordeaux, France
    2. Aquitaine Institute of Cognitive and Integrative Neurosciences, National Center for Scientific Research, Bordeaux, France
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  • Veerle Baekelandt PhD,

    1. Laboratory for Neurobiology and Gene Therapy, Catholic University, Leuven, Belgium
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  • Erwan Bezard PhD,

    Corresponding author
    1. Institute of Neurodegenerative Diseases, UMR 5293, F-33000 Bordeaux, France, National Center for Scientific Research, Bordeaux, France
    2. Neurology Service, Bordeaux University Hospital Center, Pessac, France
    • Institute of Neurodegenerative Diseases, UMR 5293, F-33000 Bordeaux, France, University of Bordeaux, Bordeaux, France
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  • Pierre-Olivier Fernagut PhD

    1. Institute of Neurodegenerative Diseases, UMR 5293, F-33000 Bordeaux, France, University of Bordeaux, Bordeaux, France
    2. Institute of Neurodegenerative Diseases, UMR 5293, F-33000 Bordeaux, France, National Center for Scientific Research, Bordeaux, France
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Address correspondence to Dr Bezard, CNRS UMR 5293, Institute of Neurodegenerative Diseases, Université Bordeaux Segalen, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. E-mail: erwan.bezard@u-bordeaux2.fr

Abstract

Dopamine dysregulation syndrome shares some core behavioral features with psychostimulant addiction, suggesting that dopamine replacement therapy can acquire psychostimulantlike properties in some patients with Parkinson disease (PD). We here report strong experimental evidence supporting this hypothesis in an α-synuclein rat model of PD. Although levodopa had no effect in controls, it acquired 2 prominent psychostimulantlike properties in Parkinsonian rats: (1) it produced intense reward on its own and in parallel (2) decreased interest in other nondrug reward. These 2 effects may combine to explain the addictive use of levodopa after loss of midbrain dopamine neurons in some PD patients. Ann Neurol 2013;74:140–144

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