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

BackgroundCognitive 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.MethodsThirty-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.ResultsThe 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.ConclusionsThe 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.