Compulsive drug use linked to sensitized ventral striatal dopamine transmission.
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).


CONCLUSIONS
This provides evidence that links sensitization of ventral striatal circuitry in humans to compulsive drug use.
Reta Lila Weston Institute of Neurological Studies and the National Hospital for Neurology and Neurosurgery, London, United Kingdom.
Andrew H
AH
Evans
Nicola
N
Pavese
Andrew D
AD
Lawrence
Yen F
YF
Tai
Silke
S
Appel
Miroslava
M
Doder
David J
DJ
Brooks
Andrew J
AJ
Lees
Paola
P
Piccini
D000368:Aged; D001931:Brain Mapping; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000502:physiology*; D049268:Positron-Emission Tomography; D011581:Psychological Tests; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050637:Receptors, Dopamine D3 / Q000187:drug effects; D019966:Substance-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D009435:Synaptic Transmission / Q000502:physiology
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride; D007980:Levodopa; D004298:Dopamine