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.
To 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.
Our 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.
Footnotes
Funding and Disclosure AS was supported by a Fondation pour la Recherche Médicale grant (grant number FDM20120624489). SP was supported by a Marie Sklodowska-Curie Individual European Fellowship (PIEF-GA-2012 Grant 328822) and is supported by an ATIP-Avenir starting grant (R16069JS). The study was supported by a grant from the Association Française du Syndrome de Gilles de la Tourette to YW. The funding agencies did not influence the content of the manuscript. The authors declare no competing financial interest. The Institut ďEtude de la Cognition is supported financially by the LabEx IEC (ANR-10-LABX-0087 IEC) and the IDEX PSL* (ANR-10-IDEX-0001-02 PSL*).