Dopamine D2/3 receptor availabilities and evoked dopamine release in striatum differentially predict impulsivity and novelty preference in Roman high- and low-avoidance rats.

Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n=49) of Roman high-(RHA) and low-(RLA) avoidance rats using single photon emission computed tomography to concurrently measure in-vivo striatal D2/3R availability and amphetamine- (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the dopamine-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex-vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the five-choice serial reaction time task, and D2/3R availability in ventral striatum (VST) and extend this relationship to D2/3R levels measured in dorsal striatum (DST). Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in DST and VST. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high impulsive/novelty-preferring RHA animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, dopamine-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.