Striatal Dopamine D₂/D₃Receptors Mediate Response Inhibition and Related Activity in Frontostriatal Neural Circuitry in Humans

Abstract

Impulsive behavior is thought to reflect a trait-like 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 blood oxygen level-dependent functional magnetic resonance imaging (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.

The effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress

“…It could therefore be hypothesized that processes relating to response inhibition are particularly vulnerable to stress in key stages of development. Performance on inhibitory control tests has been associated with both D2 receptor availability and childhood trauma in previous studies (Ghahremani et al., 2012; Marshall et al., 2016) but the more precise effect of stress on the functioning of cortico‐striatal circuitry and on cognitive function remains to be elucidated.…”

Adolescent Risk Taking, Cocaine Self-Administration, and Striatal Dopamine Signaling

“…For example, striatal D2/3 receptor availability is linked to trait impulsivity and behavioral disinhibition (Dalley et al, 2007;Ghahremani et al, 2012), and low striatal D2/3 levels are associated with elevated cocaine self-administration (Caine et al, 2002;Morgan et al, 2002;Nader et al, 2006). Furthermore, recent data from our laboratory show that low levels of striatal D2 receptor mRNA expression are associated with elevated risk taking in adult rats .…”

Longitudinal behavioral and fMRI‑based assessment of inhibitory control in heroin addicts on methadone maintenance treatment

“…The interaction of the supplementary motor area with the subcortical brain and brain stem nuclei then completes the inhibitory control process (39). The forehead-striatal loop, which participates in motion control and response inhibition, is of particular importance (40)(41)(42)(43)(44). The GO/NO-GO task is expected to trigger cognitive as well as behavioral inhibition.…”