Striatal Dopamine D2/D3Receptors Mediate Response Inhibition and Related Activity in Frontostriatal Neural Circuitry in Humans
Open accessAbstract
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 D 2-like receptors have been linked with impulsive behavior and behavioral inhibition in rodents, a role for D 2-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 D 2/D 3 dopamine receptor ligand [18 F]fallypride and BOLD fMRI while they performed the Stop-signal Task, a test of response inhibition. Striatal dopamine D 2/D 3 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 D 2/D 3 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 D 2-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.
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Increased Dopamine D2/3-receptor availability in the striatum is associated with better Stop-signal task performance (shorter SSRT) and correlates positively with inhibition-related activation of the dorsal caudate and putamen.
“Increased Dopamine D2/3-receptor availability in the striatum is associated with better Stop-signal task performance, i.e., shorter stop-signal reaction time (SSRT), and correlates positively with inhibition-related activation of the dorsal caudate and putamen (Ghahremani et al., 2012).”
From Response Inhibition and Interference Control in Obsessive–Compulsive Spectrum Disorders (2014) · cites this paper as Ghahremani et al., 2012
The Results section reports that greater caudate and putamen D2/D3-receptor availability was associated with shorter SSRT. It also reports a positive correlation with stopping-related activation in the caudate, but explicitly says this correlation was not found in the putamen. Page numbers are unavailable in our copy. (LLM, conf=0.92)
Experimental — accuracy not yet measuredImaging studies of impulsive behavior in healthy controls report mixed results on the relationship between impulsivity or response inhibition and D2 BPND/delta BPND.
“Imaging studies of impulsive behavior in healthy controls report mixed results. While some studies found an inverse relationship between measures of impulsivity or response inhibition and D2 BPND and delta BPND, other studies showed the opposite (Buckholtz et al., 2010; Ghahremani et al., 2012; Oswald et al., 2007; Reeves et al., 2012).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Ghahremani et al., 2012
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References 70 · Cited by 227
Research works printed but not linked: 2
- First MB Spitzer RL Gibbon M Williams J 1996 Structured Clinical Interview for DSM-IV Axis I Disorders- Patient Edition (SCID-IP, Version 2.0) New York, NY Biometrics Research Department, New York State Psychiatric Institute
- Li CS Yan P Sinha R Lee TW 2008b Subcortical processes of motor response inhibition during a stop signal task NeuroImage 41 1352 1363 18485743 PMC2474693
- Authors
- Ghahremani, D. G., Lee, B., Robertson, C. L., Tabibnia, G., Morgan, A. T., De Shetler, N., Brown, A. K., Monterosso, J. R., Aron, A. R., Mandelkern, M. A., Poldrack, R. A., & London, E. D.
- Affiliations
- University of California, Los Angeles (US)
- Carnegie Mellon University (US)
- University of Southern California (US)
- University of California San Diego (US)
- University of California, Irvine (US)
- The University of Texas at Austin (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-05-23
- Volume
- 32
- Issue
- 21
- Pages
- 7316-7324
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3517177
- OpenAlex
- W2060946807
- Cited by
- 227
- References
- 70
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 3 · 2023: 9 · 2022: 12 · 2021: 15 · 2020: 14 · 2019: 15 · 2018: 21 · 2017: 21 · 2016: 22 · 2015: 17 · 2014: 33 · 2013: 26 · 2012: 2
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Marjorie M. Greene Trust
- National Institutes of Health (KL2TR000122, DA024853, DA 022539)
- National Institute on Drug Abuse (RL1DA024853, P20DA022539, R01DA020726)
- National Institute of Dental and Craniofacial Research (UL1DE019580)
- National Center for Research Resources ((M01 RR00865), M01RR000865)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- dopamine D2/D3 receptors, response inhibition, impulsive behavior, frontostriatal circuits, striatum, caudate nucleus, putamen, [18F]fallypride, stop-signal task, behavioral inhibition, neural control of behavior
- MeSH terms
- Adult, Benzamides, Corpus Striatum, Female, Fluorine Radioisotopes, Frontal Lobe, Humans, Magnetic Resonance Imaging, Male, Neural Inhibition, Neural Pathways, Psychomotor Performance, Pyrrolidines, Receptors, Dopamine D2, Positron-Emission Tomography, Receptors, Dopamine D3, Functional Neuroimaging
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