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

Abstract

The nucleus accumbens core (NAc core) is involved in regulating stress and shaping reward seeking behaviors. Multiple neuromodulators, including dynorphin/kappa opioid receptor (KOR) and dopamine systems, converge in this area to influence behavioral 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 behavior is regionally specific and these rostro‐caudal differences are likely driven by greater control of KORs over dopamine inhibition in the caudal compared to rostral subregion. Given the importance of NAc core, particularly the interaction between KORs and dopamine, in regulating reward seeking behaviors 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 to 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.

Transmembrane transporter proteins: Capturing transport in motion

“…The dopaminergic terminals receive input from dynorphin via kappa opioid receptors (KOR) 6 . In the study by Karkhanis et al, 7 the impact of KOR activation on dopamine (DA) release and uptake in the NAc core is examined. The findings reveal regional differences along the rostro‐caudal axis in how KOR regulates dopamine release.…”

Welcome to Basic & Clinical Pharmacology & Toxicology 2024

“…As we embark on the new year, we invite you to explore the wealth of knowledge and exciting content our journal offers. In 2023, we published three Special Collections from focused conferences supported by the Nordic Association for the Publication of Basic and Clinical Pharmacology and Toxicology, including Adhesion G‐Protein‐coupled Receptors, 1–10 Transmembrane Transporter Proteins: Catching Transport in Motion 11–19 and Advancing Deprescribing: Learnings from the first International Conference on Deprescribing 20–31 . The second part of the latter Special Collection will appear in the January 2024 issue.…”