Kappa opioid receptor agonist U50,488 inhibits dopamine more in caudal than rostral nucleus accumbens core

The nucleus accumbens (NAc) core is involved in regulating stress and shaping reward seeking behaviours. Multiple neuromodulators, including dynorphin/kappa opioid receptor (KOR) and dopamine systems, converge in this area to influence behavioural outcomes. KOR activation acutely inhibits dopamine release and chronically depresses overall dopamine transmission. Recently, studies in the NAc shell have revealed that the impact of KOR activation on behaviour is regionally specific, and these rostro-caudal differences are likely driven by greater control of KORs over dopamine inhibition in the caudal compared with rostral subregion. Given the importance of NAc core, particularly the interaction between KORs and dopamine in regulating reward seeking behaviours, we examined the impact of KOR activation on dopamine release and uptake along the rostro-caudal axis in the NAc core of male and female mice. Using ex vivo fast scan cyclic voltammetry, we observed that KOR mediated inhibition of dopamine release was significantly greater in caudal compared with rostral NAc core with no significant sex differences observed. These data suggest that KORs regulate dopamine release differentially along the rostro-caudal axis, providing a new axis on which to examine the process by which the KOR/dopamine system controls reward encoding.

Automated summary

The nucleus accumbens (NAc) core plays a role in regulating stress and shaping reward seeking behaviours. The activation of kappa opioid receptor (KOR) inhibits dopamine release and transmission, and this impact is regionally specific in the NAc shell. The inhibition of dopamine release by KOR is greater in the caudal compared to the rostral subregion of NAc core, suggesting a differential regulation along the rostro-caudal axis.