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

Lieneke Katharina Janssen, Guillaume Sescousse, Mahur Melina Hashemi, Monique Harmina Maria Timmer, Niels Peter ter Huurne, Dirk Everdina Maria Geurts, Roshan Cools

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. The aim of the present study is to triangulate dopamine, reversal learning, and pathological gambling. 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. 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. These data demonstrate that pathological gambling is associated with a dopamine-related anomaly in reversal learning from reward and punishment.