Shu Zhan, Taylor I Mitch, Walters Seth H, Michael Adrian C
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
Eur J Neurosci. 2014 Jul;40(2):2320-8. doi: 10.1111/ejn.12604. Epub 2014 Apr 26.
The dopamine (DA) terminal fields in the rat dorsal striatum (DS) and nucleus accumbens core (NAcc) are organized as patchworks of domains that exhibit distinct kinetics of DA release and clearance. The present study used fast-scan cyclic voltammetry recordings of electrically evoked DA overflow to test the hypothesis that nomifensine might exhibit domain-dependent actions within the NAcc, as we previously found to be the case within the DS. Within the NAcc, nomifensine preferentially enhanced evoked DA overflow in the slow domains compared with the fast domains. To seek a kinetic explanation for nomifensine's selective actions, we quantified the apparent KM of DA clearance by numerically evaluating the derivative of the descending phase of the DA signal after the end of the stimulus. For comparison, we likewise quantified the apparent KM in the domains of the DS. As expected, because it is a competitive inhibitor, nomifensine significantly increased the apparent KM in both the fast and slow domains of both the NAcc and DS. However, our analysis also led to the novel finding that nomifensine preferentially increases the apparent KM in the NAcc compared with the DS; the apparent KM increased by ~500% in the NAcc and by ~200% in the DS.
大鼠背侧纹状体（DS）和伏隔核核心（NAcc）中的多巴胺（DA）终末场被组织成具有不同DA释放和清除动力学的区域拼凑物。本研究使用电诱发DA溢出的快速扫描循环伏安法记录来检验诺米芬辛可能在NAcc内表现出区域依赖性作用的假设，正如我们之前在DS内发现的情况一样。在NAcc内，与快速区域相比，诺米芬辛优先增强了慢速区域中诱发的DA溢出。为了寻找诺米芬辛选择性作用的动力学解释，我们通过数值评估刺激结束后DA信号下降阶段的导数来量化DA清除的表观KM。为了进行比较，我们同样量化了DS区域中的表观KM。正如预期的那样，由于它是一种竞争性抑制剂，诺米芬辛显著增加了NAcc和DS的快速和慢速区域中的表观KM。然而，我们的分析还得出了一个新发现，即与DS相比，诺米芬辛优先增加NAcc中的表观KM；NAcc中的表观KM增加了约500%，而DS中增加了约200%。
