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Compulsive drug use linked to sensitized ventral striatal dopamine transmission

Authors

  • Andrew H. Evans FRACP,

    1. Reta Lila Weston Institute of Neurological Studies and the National Hospital for Neurology and Neurosurgery, London, United Kingdom
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    • A.H.E. and N.P. contributed equally to this study.

  • Nicola Pavese MD,

    1. MRC Clinical Sciences Centre and Division of Neurosciences, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
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    • A.H.E. and N.P. contributed equally to this study.

  • Andrew D. Lawrence PhD,

    1. MRC Cognition and Brain Sciences Unit, Cambridge, United Kingdom
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  • Yen F. Tai MRCP,

    1. MRC Clinical Sciences Centre and Division of Neurosciences, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
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  • Silke Appel MD,

    1. Reta Lila Weston Institute of Neurological Studies and the National Hospital for Neurology and Neurosurgery, London, United Kingdom
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  • Miroslava Doder,

    1. MRC Clinical Sciences Centre and Division of Neurosciences, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
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  • David J. Brooks MD, FRCP, DSc,

    1. MRC Clinical Sciences Centre and Division of Neurosciences, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
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  • Andrew J. Lees MD, FRCP,

    1. Reta Lila Weston Institute of Neurological Studies and the National Hospital for Neurology and Neurosurgery, London, United Kingdom
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  • Paola Piccini MD, PhD

    Corresponding author
    1. MRC Clinical Sciences Centre and Division of Neurosciences, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
    • MRC Clinical Sciences Centre and Division of Neurosciences, Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 ONN, United Kingdom
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Abstract

Objective

A small group of Parkinson's disease (PD) patients compulsively use dopaminergic drugs despite causing harmful social, psychological, and physical effects and fulfil core Diagnostic and Statistical Manual (of Mental Disorders) Fourth Edition criteria for substance dependence (dopamine dysregulation syndrome [DDS]). We aimed to evaluate levodopa-induced dopamine neurotransmission in the striatum of patients with DDS compared with PD control patients.

Methods

We used a two-scan positron emission tomography protocol to calculate the percentage change in 11C-raclopride binding potential from a baseline withdrawal (off drug) state to the binding potential after an oral dose of levodopa. We related the subjective effects of levodopa to the effects on endogenous dopamine release of a pharmacological challenge with levodopa in eight control PD patients and eight patients with DDS.

Results

PD patients with DDS exhibited enhanced levodopa-induced ventral striatal dopamine release compared with levodopa-treated patients with PD not compulsively taking dopaminergic drugs. The sensitized ventral striatal dopamine neurotransmission produced by levodopa in these individuals correlated with self-reported compulsive drug “wanting” but not “liking” and was related to heightened psychomotor activation (punding).

Interpretation

This provides evidence that links sensitization of ventral striatal circuitry in humans to compulsive drug use. Ann Neurol 2006

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