Impulsivity, reward sensitivity, and dopamine 2/3 receptors availability in people with cocaine use disorder: A [11C]PHNO PET study.

Impulsivity and altered reward sensitivity are core features of cocaine use disorder (CUD). The Barratt Impulsiveness Scale (BIS-11) and the Behavioral Inhibition System/Activation System (BIS/BAS) capture individual differences in impulsive tendencies and reward responsiveness and may provide insight into addictive disorders. Although dopaminergic dysfunction is a hallmark of CUD, how dopamine D2/3 receptor availability relates to impulsivity and motivational traits remains incompletely understood. We compared impulsivity, appetitive, and aversive measures between individuals with CUD (n = 15) and healthy controls (HC; n = 14). Dopamine D2/3 receptor availability was quantified using the non-displaceable binding potential (BPND) of [¹¹C]PHNO across specific regions. Group differences in psychometric measures and associations between BIS-11 and BIS/BAS subscales and regional BPND were examined, and group × BPND interaction models were used to test differences in dopamine-behavior relationships. CUD individuals exhibited significantly higher impulsivity across all domains (all FDR-p ≤ 0.03). In the HC group, appetitive and aversive motive scores were significantly associated with BPND across multiple regions, including the putamen, pallidum, ventral striatum, caudate, amygdala, and thalamus. These associations were absent in CUD. Significant group × BPND interactions revealed differences in dopamine-impulsivity coupling in the amygdala, pallidum, and putamen. We concluded that CUD is characterized by elevated impulsivity and a disruption of the normative coupling between dopamine D2/3 receptor availability and impulsivity-related features. These findings suggest that impulsivity in CUD reflects not only heightened behavioral tendencies but also altered dopaminergic regulation, suggesting dopamine-behavior decoupling as a potential neurobiological marker in CUD.