Department of Psychology, Binghamton University-SUNY, Binghamton, New York, USA.
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Basic Clin Pharmacol Toxicol. 2023 Nov;133(5):526-534. doi: 10.1111/bcpt.13929. Epub 2023 Aug 22.
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.
伏隔核（NAc）核心参与调节应激和塑造奖励寻求行为。包括强啡肽/κ 阿片受体（KOR）和多巴胺系统在内的多种神经调质汇聚在这一区域，影响行为结果。KOR 的激活会急性抑制多巴胺的释放，并长期抑制整体多巴胺传递。最近，NAc 壳的研究揭示了 KOR 激活对行为的影响具有区域特异性，这些前后差异可能是由于与前区相比，后区 KOR 对多巴胺抑制的控制更强所致。鉴于 NAc 核心的重要性，特别是 KOR 和多巴胺在调节奖励寻求行为中的相互作用，我们研究了 KOR 激活对雄性和雌性小鼠 NAc 核心沿前后轴多巴胺释放和摄取的影响。使用离体快速扫描循环伏安法，我们观察到 KOR 介导的多巴胺释放抑制在 NAc 核心的后区比前区更显著，且未观察到显著的性别差异。这些数据表明，KOR 沿前后轴调节多巴胺释放的方式不同，为研究 KOR/多巴胺系统控制奖励编码的过程提供了一个新的轴。
