Compulsive Drug Use Linked to Sensitized

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 dopa-mine 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 neurotransmis-sion 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;59:852–858 Dopaminergic drug therapy is a highly effective symp-tomatic treatment for the motor disability of Parkinson’s disease (PD).1 However, antiparkinson dopaminergic medications have the potential to be compulsively used by a small group of susceptible individuals with PD.2–4 These individuals typically request extra drugs and com-plain of developing tolerance to the effects of the drugs despite the external appearance of being well medicated and displaying disabling drug-induced abnormal invol-untary movements (dyskinesias).2,3 This syndrome is called “dopamine dysregulation”4 (DDS), and many of these individuals fulfil core Diagnostic and Statistica