Striatal D 1 - and D 2 -type Dopamine Receptors Are Linked to Motor Response Inhibition in Human Subjects

• Published in: The Journal of neuroscience Vol. 35; no. 15; pp. 5990 - 5997
• Main Authors: Robertson, Chelsea L., Ishibashi, Kenji, Mandelkern, Mark A., Brown, Amira K., Ghahremani, Dara G., Sabb, Fred, Bilder, Robert, Cannon, Tyrone, Borg, Jacqueline, London, Edythe D.
• Format: Journal Article
• Language: English
• Published: 15.04.2015
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.4850-14.2015

Motor response inhibition is mediated by neural circuits involving dopaminergic transmission; however, the relative contributions of dopaminergic signaling via D 1 - and D 2 -type receptors are unclear. Although evidence supports dissociable contributions of D 1 - and D 2 -type receptors to response inhibition in rats and associations of D 2 -type receptors to response inhibition in humans, the relationship between D 1 -type receptors and response inhibition has not been evaluated in humans. Here, we tested whether individual differences in striatal D 1 - and D 2 -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 D 1 - and D 2 -type receptor availability [binding potential referred to nondisplaceable uptake (BP ND )], measured using positron emission tomography with [ 11 C]NNC-112 and [ 18 F]fallypride, respectively. Stop-signal reaction time was negatively correlated with D 1 - and D 2 -type BP ND 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 D 1 - and D 2 -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 D 1 - and D 2 -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.