Ventral Striatal D2/3 Receptor Availability Is Associated with Impulsive Choice Behavior As Well As Limbic Corticostriatal Connectivity

Background: Low dopamine D-2/3 receptor availability in the nucleus accumbens shell is associated with highly impulsive behavior in rats as measured by premature responses in a cued attentional task. However, it is unclear whether dopamine D-2/3 receptor availability in the nucleus accumbens is equally linked to intolerance for delayed rewards, a related form of impulsivity. Methods: We investigated the relationship between D-2/3 receptor availability in the nucleus accumbens and impulsivity in a delay-discounting task where animals must choose between immediate, small-magnitude rewards and delayed, largermagnitude rewards. Corticostriatal D-2/3 receptor availability was measured in rats stratified for high and low impulsivity using in vivo [F-18] fallypride positron emission tomography and ex vivo [H-3] raclopride autoradiography. Resting-state functional connectivity in limbic corticostriatal networks was also assessed using fMRI. Results: Delay-discounting task impulsivity was inversely related to D-2/3 receptor availability in the nucleus accumbens core but not the dorsal striatum, with higher D-2/3 binding in the nucleus accumbens shell of high-impulsive rats compared with low-impulsive rats. D(2/)3 receptor availability was associated with stronger connectivity between the cingulate cortex and hippocampus of high-vs low-impulsive rats. Conclusions: We conclude that delay-discounting task impulsivity is associated with low D-2/3 receptor binding in the nucleus accumbens core. Thus, two related forms of waiting impulsivity-premature responding and delay intolerance in a delay-ofreward task-implicate an involvement of D-2/3 receptor availability in the nucleus accumbens shell and core, respectively. This dissociation may be causal or consequential to enhanced functional connectivity of limbic brain circuitry and hold relevance for attention-deficit/hyperactivity disorder, drug addiction, and other psychiatric disorders.