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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
Evans, A.H. and Pavese, N. and Lawrence, A.D. and Tai, Y.F. and Appel, S. and Doder, M. and Brooks, D.J. and Lees, A.J. and Piccini, P. (2006) Compulsive drug use linked to sensitized ventral striatal dopamine transmission. Annals of Neurology, 59 (5). pp. 852-858. ISSN 03645134.
