Striatal dopamine D₂/D₃ receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans.

TitleStriatal dopamine D₂/D₃ receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans.
Publication TypeJournal Article
Year of Publication2012
AuthorsGhahremani, DG, Lee B, Robertson CL, Tabibnia G, Morgan AT, De Shetler N, Brown AK, Monterosso JR, Aron AR, Mandelkern MA, Poldrack RA, London ED
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume32
Issue21
Pagination7316-24
Date Published2012 May 23
ISSN1529-2401
KeywordsAdult, Benzamides, Corpus Striatum, Female, Fluorine Radioisotopes, Frontal Lobe, Functional Neuroimaging, Humans, Magnetic Resonance Imaging, Male, Neural Inhibition, Neural Pathways, Positron-Emission Tomography, Psychomotor Performance, Pyrrolidines, Receptors, Dopamine D2, Receptors, Dopamine D3
Abstract

Impulsive behavior is thought to reflect a traitlike characteristic that can have broad consequences for an individual's success and well-being, but its neurobiological basis remains elusive. Although striatal dopamine D₂-like receptors have been linked with impulsive behavior and behavioral inhibition in rodents, a role for D₂-like receptor function in frontostriatal circuits mediating inhibitory control in humans has not been shown. We investigated this role in a study of healthy research participants who underwent positron emission tomography with the D₂/D₃ dopamine receptor ligand [¹⁸F]fallypride and BOLD fMRI while they performed the Stop-signal Task, a test of response inhibition. Striatal dopamine D₂/D₃ receptor availability was negatively correlated with speed of response inhibition (stop-signal reaction time) and positively correlated with inhibition-related fMRI activation in frontostriatal neural circuitry. Correlations involving D₂/D₃ receptor availability were strongest in the dorsal regions (caudate and putamen) of the striatum, consistent with findings of animal studies relating dopamine receptors and response inhibition. The results suggest that striatal D₂-like receptor function in humans plays a major role in the neural circuitry that mediates behavioral control, an ability that is essential for adaptive responding and is compromised in a variety of common neuropsychiatric disorders.

DOI10.1002/hbm.22021
Alternate JournalJ. Neurosci.