Sulpiride modulates striatal BOLD signal during the manipulation of information in working memory

Dopamine plays an important role in working memory. It has been hypothesized that D1 receptor signalling in the prefrontal cortex supports the stable maintenance of information in working memory, while D2 receptor signalling in the striatum facilitates the flexible updating and manipulation of new information in working memory. In the present study we tested the hypothesis that striatal dopamine is important for the manipulation of information in working memory in a pharmacological, event-related fMRI study. Twenty healthy human subjects were scanned twice, once after placebo and once after sulpiride 400mg, a selective D2 receptor antagonist, while performing a working memory task requiring different levels of manipulation. We observed a significant correlation between sulpiride plasma levels and BOLD signal related to manipulation bilaterally in the putamen, suggesting a dose-dependent effect of D2 antagonism on a striatally-based manipulation process. These effects on BOLD signal 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 PFC. 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.