Does partial blockade of dopamine D2 receptors with Amisulpride cause anhedonia? An experimental study in healthy volunteers

Background: Anhedonia is a frequent cause of functional impairment in psychosis. Although it is plausible that medication-induced D2 receptor blockade could diminish hedonic responding, there is little experimental research testing this hypothesis in humans.Methods: To inspect possible effects of partial D2 blockade on hedonic experiences, we administered 300 mg of Amisulpride or placebo to 85 participants in a randomized, double-blind, placebo-controlled trial. Participants were then subjected to an emotional evocation task utilizing standardized pictorial pleasant, neutral, and unpleasant stimuli.Results: We observed lower positivity ratings in the Amisulpride group compared to placebo across all stimulus categories (p = .026, f = 0.25) and no group differences in negativity or arousal ratings. The Amisulpride group also showed lower electrodermal responses across all stimulus categories compared to placebo (p = .017, f = 0.27). The electrodermal response was especially diminished for pleasant stimuli.Conclusion: We interpret our findings as evidence that D2 blockade via Amisulpride can reduce at-the-moment hedonic responsivity in healthy volunteers. If these results can be confirmed in drug-naive clinical samples, this would indicate that antipsychotic medication contributes to clinical anhedonia, probably via antagonistic effects at the dopamine D2 receptor.

Automated summary

This study investigated the effects of partial D2 receptor blockade on hedonic experiences by administering 300 mg of Amisulpride or placebo to 85 participants. The results showed that the Amisulpride group had lower positivity ratings and lower electrodermal responses compared to the placebo group across all stimulus categories. These findings suggest that D2 receptor blockade can reduce immediate hedonic responsivity in healthy volunteers.