The dopamine D2 receptor antagonist sulpiride modulates striatal BOLD signal during the manipulation of information in working memory

RATIONALE: Dopamine (DA) plays an important role in working memory. However, the precise functions supported by different DA receptor subtypes in different neural regions remain unclear. OBJECTIVE: The present study used pharmacological, event-related fMRI to test the hypothesis that striatal dopamine is important for the manipulation of information in working memory. METHODS: Twenty healthy human subjects were scanned twice, once after placebo and once after sulpiride 400 mg, a selective DA D2 receptor antagonist, while performing a verbal working memory task requiring different levels of manipulation. RESULTS: Whilst there was no overall effect of sulpiride on task-dependent activation, individual variation in sulpiride plasma levels predicted the effect of working memory manipulation on activation in the putamen, suggesting a dose-dependent effect of DA antagonism on a striatally based manipulation process. These effects occurred in the context of a drug-induced improvement in performance on trials requiring the manipulation of information in working memory but not on simple retrieval trials. No significant drug effects were observed in the prefrontal cortex. CONCLUSIONS: These results support models of dopamine function that posit a ‘gating’ function for dopamine D2 receptors in the striatum, which enables the flexible updating and manipulation of information in working memory.