Abnormal modulation of reward versus punishment learning by a dopamine D2-receptor antagonist in pathological gamblers

Abstract

Rationale: Pathological gambling has been associated with dopamine transmission abnormalities, in particular dopamine D2-receptor deficiency, and reversal learning deficits. Moreover, pervasive theoretical accounts suggest a key role for dopamine in reversal learning. However, there is no empirical evidence for a direct link between dopamine, reversal learning and pathological gambling. Objective: The aim of the present study is to triangulate dopamine, reversal learning, and pathological gambling. Methods: Here, we assess the hypothesis that pathological gambling is accompanied by dopamine-related problems with learning from reward and punishment by investigating effects of the dopamine D2-receptor antagonist sulpiride (400 mg) on reward- and punishment-based reversal learning in 18 pathological gamblers and 22 healthy controls, using a placebo-controlled, double-blind, counter-balanced design. Results: In line with previous studies, blockade of D2 receptors with sulpiride impaired reward versus punishment reversal learning in controls. By contrast, sulpiride did not have any outcome-specific effects in gamblers. Conclusion: These data demonstrate that pathological gambling is associated with a dopamine-related anomaly in reversal learning from reward and punishment.