Pathological gambling associated with dopamine agonists: predisposing neurobiology investigated with fMRI

Treatment with dopamine receptor agonists (DA) has been associated with pathological gambling (PG) secondary to medication in previously unaffected patients with Parkinson's disease or restless legs syndrome (RLS). In a within-subjects design we investigated the underlying neurobiology in RLS patients using functional magnetic resonance imaging (fMRI). We scanned 12 female RLS patients without a history of PG. All patients were scanned twice: once while taking their regular medication with low dose DA and once after a washout phase interval. They performed an established gambling task involving expectation and receipt or omission of monetary rewards at different levels of probabilities. Upon expectation of rewards, reliable ventral striatal activation was detected only when patients were on, but not when patients were off medication. Upon receipt or omission of rewards, the observed ventral striatal signal under medication differed markedly from its predicted pattern which by contrast was apparent when patients were off medication. Orbitofrontal activation was not affected by medication. Chronic DA medication changed the neural signaling of reward expectation predisposing the dopaminergic reward system to mediate an increased appetitive drive and led to markedly changed neural processing of negative consequences. Intact orbitofrontal functioning, potentially moderating impulse control, may explain why none of the patients actually developed PG.