Department of Psychology, University of Illinois at Chicago, Chicago, IL 60607, USA.
Psychopharmacology (Berl). 2010 Jun;210(2):241-52. doi: 10.1007/s00213-010-1836-5. Epub 2010 Apr 7.
Kappa opioid receptors (KORs) have been implicated in depressive-like states associated with chronic administration of drugs of abuse and stress. Although KOR agonists decrease dopamine in the nucleus accumbens (NAc), KOR modulation of phasic dopamine release in the core and shell subregions of the NAc-which have distinct roles in reward processing-remains poorly understood.
Studies were designed to examine whether the time course of effects of KOR activation on phasic dopamine release in the NAc core or shell are similar to effects on motivated behavior.
The effect of systemic administration of the KOR agonist salvinorin A (salvA)-at a dose (2.0 mg/kg) previously determined to have depressive-like effects-was measured on electrically evoked phasic dopamine release in the NAc core or shell of awake and behaving rats using fast scan cyclic voltammetry. In parallel, the effects of salvA on intracranial self-stimulation (ICSS) and sucrose-reinforced responding were assessed. For comparison, a threshold dose of salvA (0.25 mg/kg) was also tested.
The active, but not threshold, dose of salvA significantly decreased phasic dopamine release without affecting dopamine reuptake in the NAc core and shell. SalvA increased ICSS thresholds and significantly lowered breakpoint on the progressive ratio schedule, indicating a decrease in motivation. The time course of the KOR-mediated decrease in dopamine in the core was qualitatively similar to the effects on motivated behavior.
These data suggest that the effects of KOR activation on motivation are due, in part, to inhibition of phasic dopamine signaling in the NAc core.
κ 阿片受体（KOR）与慢性滥用药物和应激相关的抑郁样状态有关。尽管 KOR 激动剂会减少伏隔核（NAc）中的多巴胺，但 KOR 对 NAc 核心和壳区中相位多巴胺释放的调制——它们在奖励处理中具有不同的作用——仍然知之甚少。
设计这些研究旨在检查 KOR 激活对 NAc 核心或壳区相位多巴胺释放的影响是否与对动机行为的影响相似。
使用快速扫描循环伏安法，在清醒和行为大鼠中，测量系统给予 KOR 激动剂沙利福林 A（salvA）（先前确定具有抑郁样作用的剂量 2.0mg/kg）对 NAc 核心或壳区电诱发相位多巴胺释放的影响。同时，评估 salvA 对颅内自我刺激（ICSS）和蔗糖强化反应的影响。为了比较，还测试了 salvA 的阈值剂量（0.25mg/kg）。
活性但不是阈值剂量的 salvA 显著降低了 NAc 核心和壳区的相位多巴胺释放，而不影响多巴胺再摄取。SalvA 增加了 ICSS 阈值，并显著降低了递增比率方案中的断点，表明动机降低。KOR 介导的多巴胺在核心中的减少的时间过程与对动机行为的影响在性质上相似。
这些数据表明，KOR 激活对动机的影响部分归因于 NAc 核心中相位多巴胺信号的抑制。
