Compulsive drug use linked to sensitized ventral striatal dopamine transmission

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Andrew H. Evans, UCL
  • ,
  • Nicola Pavese
  • Andrew D. Lawrence, MRC Cognition and Brain Sciences Unit, Cambridge
  • ,
  • Yen F. Tai, Hammersmith Hospital
  • ,
  • Silke Appel, UCL
  • ,
  • Miroslava Doder, Hammersmith Hospital
  • ,
  • David J. Brooks
  • Andrew J. Lees, UCL
  • ,
  • Paola Piccini, Hammersmith Hospital

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 "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.

Original languageEnglish
JournalAnnals of Neurology
Volume59
Issue5
Pages (from-to)852-858
Number of pages7
ISSN0364-5134
DOIs
Publication statusPublished - 1 May 2006
Externally publishedYes

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