Specific effect of dopamine partial agonist on counterfactual learning: evidence from Gilles de la Tourette syndrome

Abstract

The dopamine partial agonist aripiprazole is increasingly used to treat pathologies for which other antipsychotics are indicated because it displays fewer side effects, such as sedation and depression-like symptoms, than other dopamine receptor antagonists. Previously, we showed that aripiprazole may protect motivational function by preserving reinforcement-related signals used to sustain reward-maximization behaviour in a simple action-outcome learning task. However, the effect of aripiprazole on more cognitive facets of human reinforcement learning, such as learning from the hypothetical outcomes of alternative courses of action (i.e., counterfactual learning), is unknown.\n\nTo test the influence of aripiprazole on counterfactual learning, we administered a reinforcement-learning task that involves both direct learning from obtained outcomes and indirect learning from forgone outcomes to two groups of Gilles de la Tourette (GTS) patients, one consisting of patients who were completely unmedicated and the other consisting of patients who were receiving aripiprazole monotherapy, and to healthy subjects. We replicated a previous finding showing that aripiprazole does not affect direct learning from obtained outcomes in GTS. We also found that whereas learning performance improved in the presence of counterfactual feedback in both healthy controls and unmedicated GTS patients, this was not the case in aripiprazole-medicated GTS patients.\n\nOur results suggest that whereas aripiprazole preserves direct learning of action-outcome associations, it may impair more complex inferential processes, such as counterfactual learning, from forgone outcomes.