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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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Department of Psychology, University of British Columbia, Vancouver. Electronic address:
Translational 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.
Department of Psychiatry, Bangor University, Bangor, United Kingdom.
Department 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.


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

[Indexed for MEDLINE]

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