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.

Keywords: PET imaging; dopamine; impulsivity.

Copyright © 2015 the authors 0270-6474/15/355990-08$15.00/0.

Figures

Figure 4.

Scatter plot depicting the relationship between D2-type BPND and D1-type BPND in the whole striatum; z-scores of BPND were used for presentation purposes. Table insert displays correlation coefficients, p values, and R2 values for the correlations in the whole and associative striatum.

Figure 1.

Scatter plot depicting the correlation between SSRT and D1-type BPND in the whole striatum. Table insert displays partial correlation coefficients, p values, and R2 values for the relationship between whole striatum and associative striatum D1-type BPND and SSRT, controlling for age and sex.

Figure 2.

Scatter plot depicting the correlation between SSRT and D2-type BPND in the whole striatum. Table insert displays partial correlation coefficients, p values, and R2 values for the relationship between whole striatum and associative striatum D2-type BPND and SSRT, controlling for age and sex.

Figure 3.

A, B, Voxelwise effect size maps depicting the partial correlation coefficient (r) between individual SSRT and D1-type (A) and D2-type (B) receptor BPND in the striatum, controlling for the effects of age and sex.