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首页> 外文期刊>The European Journal of Neuroscience >Region- and domain-dependent action of nomifensine
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Region- and domain-dependent action of nomifensine

机译：Nomifensine的区域和区域依赖性作用

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摘要

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.
机译：大鼠背纹状体（DS）和伏隔核核心（NAcc）中的多巴胺（DA）末端场被组织为域的拼凑物，这些域表现出不同的DA释放和清除动力学。本研究使用电诱发的DA溢出的快速扫描循环伏安法记录，以检验诺米芬新可能在NAcc中表现出域依赖性作用的假设，正如我们先前在DS中所发现的那样。与快速域相比，在慢速域中，诺非芬定优先增强诱发的DA溢出。为了寻求诺米芬辛选择性作用的动力学解释，我们通过对刺激结束后DA信号下降阶段的导数进行数值评估，量化了DA清除的表观KM。为了进行比较，我们同样量化了DS域中的表观KM。正如预期的那样，由于诺米非辛是一种竞争性抑制剂，因此在NAcc和DS的快域和慢域均显着增加了表观KM。然而，我们的分析也导致了一个新颖的发现，即与DS相比，诺米非斯汀优先增加NAcc中的表观KM。在NAcc中，表观KM增加了约500％，而在DS中则增加了约200％。

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