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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, ηp2 = .06) 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, ηp2 = .07). 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. In case these results can be confirmed in drug-naïve patients with psychosis, this could indicate that antipsychotic medication contributes to anhedonia in clinically relevant contexts, probably via antagonistic effects at the dopamine D2 receptor. |
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