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

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.