A Selective Role for Dopamine D4 Receptors in Modulating Reward Expectancy in a Rodent Slot Machine Task

  • Paul J. Cocker
    Address correspondence to Paul J. Cocker, B.Sc., University of British Columbia, Department of Psychology, 2136 West Mall, Vancouver, BC V6T 1Z4, Canada
    Department of Psychology, University of British Columbia, Vancouver
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  • Bernard Le Foll
    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
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  • Robert D. Rogers
    Department of Psychiatry, Bangor University, Bangor, United Kingdom
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  • Catharine A. Winstanley
    Department of Psychology, University of British Columbia, Vancouver
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      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.

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