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

Psychiatry Res. 2026 May 25;364:117239. doi: 10.1016/j.psychres.2026.117239. Online ahead of print.

ABSTRACT

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 D_2/3 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 D_2/3 receptor availability was quantified using the non-displaceable binding potential (BP_ND) of [¹¹C]PHNO across specific regions. Group differences in psychometric measures and associations between BIS-11 and BIS/BAS subscales and regional BP_ND were examined, and group × BP_ND 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 BP_ND across multiple regions, including the putamen, pallidum, ventral striatum, caudate, amygdala, and thalamus. These associations were absent in CUD. Significant group × BP_ND 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 D_2/3 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.

PMID:42229023 | DOI:10.1016/j.psychres.2026.117239