title: Striatal D1- and D2-type dopamine receptors are linked to motor response inhibition in human subjects.
abstract: Motor response inhibition is mediated by neural circuits involving dopaminergic transmission; however, the relative contributions of dopaminergic signaling via D1- and D2-type receptors are unclear. Although evidence supports dissociable contributions of D1- and D2-type receptors to response inhibition in rats and associations of D2-type receptors to response inhibition in humans, the relationship between D1-type receptors and response inhibition has not been evaluated in humans. Here, we tested whether individual differences in striatal D1- and D2-type receptors are related to response inhibition in human subjects, possibly in opposing ways. Thirty-one volunteers participated. Response inhibition was indexed by stop-signal reaction time on the stop-signal task and commission errors on the continuous performance task, and tested for association with striatal D1- and D2-type receptor availability [binding potential referred to nondisplaceable uptake (BPND)], measured using positron emission tomography with [(11)C]NNC-112 and [(18)F]fallypride, respectively. Stop-signal reaction time was negatively correlated with D1- and D2-type BPND in whole striatum, with significant relationships involving the dorsal striatum, but not the ventral striatum, and no significant correlations involving the continuous performance task. The results indicate that dopamine D1- and D2-type receptors are associated with response inhibition, and identify the dorsal striatum as an important locus of dopaminergic control in stopping. Moreover, the similar contribution of both receptor subtypes suggests the importance of a relative balance between phasic and tonic dopaminergic activity subserved by D1- and D2-type receptors, respectively, in support of response inhibition. The results also suggest that the stop-signal task and the continuous performance task use different neurochemical mechanisms subserving motor response inhibition.
authors: Departments of Molecular and Medical Pharmacology, and Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California 90073, and.
authors: Chelsea L
authors: CL
authors: Robertson
authors: Department of Psychiatry and Biobehavioral Sciences, The Semel Institute for Neuroscience and Human Behavior at UCLA, and Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90024.
authors: Kenji
authors: K
authors: Ishibashi
authors: Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California 90073, and Department of Physics, University of California, Irvine, Irvine, California 92697.
authors: Mark A
authors: MA
authors: Mandelkern
authors: Department of Psychiatry and Biobehavioral Sciences, The Semel Institute for Neuroscience and Human Behavior at UCLA, and.
authors: Amira K
authors: AK
authors: Brown
authors: Department of Psychiatry and Biobehavioral Sciences, The Semel Institute for Neuroscience and Human Behavior at UCLA, and.
authors: Dara G
authors: DG
authors: Ghahremani
authors: Department of Psychiatry and Biobehavioral Sciences, The Semel Institute for Neuroscience and Human Behavior at UCLA, and.
authors: Fred
authors: F
authors: Sabb
authors: Department of Psychiatry and Biobehavioral Sciences, The Semel Institute for Neuroscience and Human Behavior at UCLA, and.
authors: Robert
authors: R
authors: Bilder
authors: Psychology.
authors: Tyrone
authors: T
authors: Cannon
authors: Psychology.
authors: Jacqueline
authors: J
authors: Borg
authors: Departments of Molecular and Medical Pharmacology, and Department of Psychiatry and Biobehavioral Sciences, The Semel Institute for Neuroscience and Human Behavior at UCLA, and Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90024, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California 90073, and elondon@mednet.ucla.edu.
authors: Edythe D
authors: ED
authors: London
mesh_terms: D000328:Adult; D001549:Benzamides / Q000493:pharmacokinetics; D001552:Benzazepines / Q000493:pharmacokinetics; D001572:Benzofurans / Q000493:pharmacokinetics; D002755:Choice Behavior; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D021621:Imaging, Three-Dimensional; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012044:Regression Analysis; D055815:Young Adult
chemical_list: D001549:Benzamides; D001552:Benzazepines; D001572:Benzofurans; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019788:Fluorodeoxyglucose F18; C077123:NNC 112; C574003:fallypride
keywords: PET imaging; dopamine; impulsivity