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 im^pairment 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-naïve clinical samples, this would indicate that antipsychotic medication contributes to clinical anhedonia, probably via antagonistic effects at the dopamine D2 receptor.