Region- and domain-dependent action of nomifensine.
Region- and domain-dependent action of nomifensine.
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DOI：
10.1111/ejn.12604
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发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
Michael AC
中科院分区：
文献类型：
--
作者：
Shu Z;Taylor IM;Walters SH;Michael AC
大鼠背侧纹状体（DS）和延髓核（NAcc）的多巴胺（DA）终末场被组织为表现出不同的DA释放和清除动力学的域拼凑。本研究使用快速扫描循环伏安法记录电诱发DA溢出测试的假设，诺米芬新可能表现出域依赖性的行动内的NAcc，因为我们以前发现的情况下，在DS。在NAcc内，与快速域相比，诺米芬辛优先增强慢域中的诱发多巴胺溢出。为了寻求动力学解释诺米芬新的选择性行动，我们量化的DA清除率的明显KM通过数值评估的衍生物的DA信号的下降阶段结束后的刺激。为了比较，我们同样量化了DS域中的表观KM。正如所预期的，因为它是竞争性抑制剂，诺米芬新显著增加了NAcc和DS的快域和慢域中的表观KM。然而，我们的分析还导致了新的发现，与DS相比，诺米芬新优先增加NAcc中的表观KM：表观KM在NAcc中增加约500%，在DS中增加约200%。
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 dopamine overflow in the slow compared to 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 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 leads to the novel finding that nomifensine preferentially increases the apparent KM in the NAcc compared to the DS: apparent KM increased by ~500% in the NAcc and ~200% in the DS.
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