The dopamine D2 receptor antagonist sulpiride modulates striatal BOLD signal during the manipulation of information in working memory.
BACKGROUND
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.
Dodds
Chris M
CM
Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK. cd317@cam.ac.uk
Clark
Luke
L
Dove
Anja
A
Regenthal
Ralf
R
Baumann
Frank
F
Bullmore
Ed
E
Robbins
Trevor W
TW
Müller
Ulrich
U
D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D003342:Corpus Striatum / Q000098:blood supply* / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010147:Pain Measurement; D011930:Reaction Time / Q000187:drug effects; D013223:Statistics as Topic; D013469:Sulpiride / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
D018492:Dopamine Antagonists; D013469:Sulpiride; D010100:Oxygen