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Brain Advance Access originally published online on June 30, 2009
Brain 2009 132(9):2396-2402; doi:10.1093/brain/awp170
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© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

At-risk for pathological gambling: imaging neural reward processing under chronic dopamine agonists

Birgit Abler1, Roman Hahlbrock1, Alexander Unrath2, Georg Grön1 and Jan Kassubek2

1 Department of Psychiatry, University of Ulm, Ulm, Germany 2 Department of Neurology, University of Ulm, Ulm, Germany

Correspondence to: Dr Birgit Abler, MD, Department of Psychiatry, University of Ulm, Leimgrubenweg 12-14, 89075 Ulm, Germany E-mail: birgit.abler{at}uni-ulm.de

Treatment with dopamine receptor agonists has been associated with impulse control disorders and 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. We scanned 12 female RLS patients without a history of PG. All patients were scanned twice: once whilst taking their regular medication with low dose dopamine receptor agonists and once after a washout phase interval. They performed an established gambling game 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 dopamine receptor agonist medication changed the neural signalling of reward expectation predisposing the dopaminergic reward system to mediate an increased appetitive drive. Even without manifest PG, chronic medication with dopamine receptor agonists led to markedly changed neural processing of negative consequences probably mediating dysfunctional learning of contingencies. Intact orbitofrontal functioning, potentially moderating impulse control, may explain why none of the patients actually developed PG. Our results support the notion of a general medication effect in patients under dopamine receptor agonists in terms of a sensitization towards impulse control disorders.

Key Words: reward; fMRI; restless legs syndrome; dopamine agonists; pathological gambling

Abbreviations: DA, dopamine agonists; PG, pathological gambling; RLS, restless legs syndrome

Received November 24, 2008. Revised February 16, 2009. Accepted May 20, 2009.


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