Dopamine is a double-edged sword: dopaminergic modulation enhances memory retrieval performance but impairs...

While memory encoding and consolidation processes have been linked with dopaminergic signaling for a long time, the role of dopamine in episodic memory retrieval remained mostly unexplored. Based on previous observations of striatal activity during memory retrieval, we used pharmacological functional magnetic resonance imaging to investigate the effects of dopamine on retrieval performance and metacognitive memory confidence in healthy humans. Dopaminergic modulation by the D2 antagonist haloperidol administered acutely during the retrieval phase improved recognition accuracy of previously learned pictures significantly and was associated with increased activity in the substantia nigra/ventral tegmental area, locus coeruleus, hippocampus, and amygdala during retrieval. In contrast, confidence for new decisions was impaired by unsystematically increased activity of the striatum across confidence levels and restricted range of responsiveness in frontostriatal networks under haloperidol. These findings offer new insights into the mechanisms underlying memory retrieval and metacognition and provide a broader perspective on the presence of memory problems in dopamine-related diseases and the treatment of memory disorders.