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Compulsive drug use linked to sensitized ventral striatal dopamine transmission
Author(s) -
Evans Andrew H.,
Pavese Nicola,
Lawrence Andrew D.,
Tai Yen F.,
Appel Silke,
Doder Miroslava,
Brooks David J.,
Lees Andrew J.,
Piccini Paola
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20822
Subject(s) - dopamine , drug , ventral striatum , medicine , psychology , neuroscience , psychiatry , striatum
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 11 C‐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