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Biol Psychiatry. 2014 May 15;75(10):817-24. doi: 10.1016/j.biopsych.2013.08.026. Epub 2013 Oct 4.

A selective role for dopamine D₄ receptors in modulating reward expectancy in a rodent slot machine task.

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  • 1Department of Psychology, University of British Columbia, Vancouver. Electronic address:
  • 2Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, University of Toronto, Toronto, Ontario, Canada; Alcohol Research and Treatment Clinic, Addiction Medicine Services, Ambulatory Care and Structured Treatments, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, Pharmacology, Family and Community Medicine, and Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
  • 3Department of Psychiatry, Bangor University, Bangor, United Kingdom.
  • 4Department of Psychology, University of British Columbia, Vancouver.



Cognitive distortions regarding gambling outcomes confer vulnerability to pathological gambling. Using a rat slot machine task (rSMT), we previously demonstrated that the nonspecific D₂ agonist quinpirole enhances erroneous expectations of reward on near-miss trials, suggesting a pivotal role for the D₂ receptor family in mediating the near-miss effect. Identifying which receptor subtype is involved could facilitate treatment development for compulsive slot machine play.


Thirty-two male Long Evans rats learned the rSMT. Three flashing lights could be set to on or off. A win was signaled if all three lights were set to on, whereas any other light pattern indicated a loss. Rats then chose between responding on the collect lever, which delivered 10 sugar pellets on win trials but a 10-second time penalty on loss trials, or to start a new trial instead. Performance was assessed following systemic administration of selective D₂, D₃, and D₄ receptor ligands.


The selective D₂ antagonist L-741,626, the D₃ antagonist SB-277011-A, and the D₃ agonist PD128,907 had no effect. In contrast, the selective D₄ agonist PD168077 partially mimicked quinpirole's effects, increasing erroneous collect responses on nonwin trials, whereas the D₄ antagonist L-745,870 improved the error rate. L-745,870 was also the only antagonist that could attenuate the deleterious effects of quinpirole.


The dopamine D₄ receptor is critically involved in signaling reward expectancy in the rSMT. The ability of L-745,870 to reduce the classification of losses as wins suggests that D₄ antagonists could be effective in treating problematic slot machine play.

© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.


Anterior cingulate; L-745,870; gambling; incentive salience; near-miss; quinpirole

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