title: Striatal dopamine D₂/D₃ receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans.
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.
authors.affiliation: Departments of Psychiatry and Biobehavioral Sciences and Molecular and Medical Pharmacology, and Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Dara G
authors.initials: DG
authors.lastname: Ghahremani
authors.forename: Buyean
authors.initials: B
authors.lastname: Lee
authors.forename: Chelsea L
authors.initials: CL
authors.lastname: Robertson
authors.forename: Golnaz
authors.initials: G
authors.lastname: Tabibnia
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Morgan
authors.forename: Natalie
authors.initials: N
authors.lastname: De Shetler
authors.forename: Amira K
authors.initials: AK
authors.lastname: Brown
authors.forename: John R
authors.initials: JR
authors.lastname: Monterosso
authors.forename: Adam R
authors.initials: AR
authors.lastname: Aron
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mandelkern
authors.forename: Russell A
authors.initials: RA
authors.lastname: Poldrack
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
mesh_terms: D000328:Adult; D001549:Benzamides; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000502:physiology*; D005260:Female; D005462:Fluorine Radioisotopes; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000502:physiology*; D059907:Functional Neuroimaging / Q000379:methods / Q000523:psychology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000523:psychology; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000502:physiology; D049268:Positron-Emission Tomography / Q000379:methods / Q000523:psychology; D011597:Psychomotor Performance / Q000502:physiology; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000378:metabolism / Q000502:physiology*; D050637:Receptors, Dopamine D3 / Q000378:metabolism / Q000502:physiology*
chemical_list: D001549:Benzamides; D005462:Fluorine Radioisotopes; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C037689:benzamide