Kappa-opioid receptor-dependent changes in dopamine and affective behavior occur differentially across the nucleus accumbens shell rostro-caudal axis

Abstract

Neural activity in the nucleus accumbens (NAc) shell has long been implicated in the regulation of negative and positive affect. Classically, the dynorphin/kappa opioid receptor (KOR) system in the NAc was believed to promote dysphoric behaviors, while dopamine release was viewed as interacting with reinforcing stimuli, and KOR-activation was known to inhibit dopamine release. Recently, however, both the KOR and dopamine systems have been shown to have differential effects across the rostro-caudal axis of the NAc shell on hedonic responses. Whether or not this is due to interactions between KORs and dopamine, and if it extends to other affective behaviors, remains to be determined. In this study, we examined in rats the relationship between the KOR and dopamine systems in both the rostral and caudal NAc shell using ex vivo fast scan cyclic voltammetry and the impact of KOR activation on affective behaviors using various assays.We found that activation of KORs in the caudal NAc shell resulted in greater dopamine inhibition, and stimulated novelty-induced rearing behavior and anxiety-like and avoidance behaviors while reducing locomotor activity. In contrast, activation of KORs in the rostral NAc shell resulted in less dopamine inhibition and actually reduced anxiety-like and avoidance behaviors. These results demonstrate that there is heterogeneity across the rostro-caudal axis of the NAc shell in the effects of KOR stimulation on affective behavior and they suggest that this might be due to differences in KOR control over dopamine inhibition.