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首页> 外文期刊>BMC Neuroscience >Presynaptic action of neurotensin on dopamine release through inhibition of D 2 receptor function
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Presynaptic action of neurotensin on dopamine release through inhibition of D 2 receptor function

机译：神经降压素通过抑制D 2受体功能对多巴胺释放的突触前作用

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Background Neurotensin (NT) is known to act on dopamine (DA) neurons at the somatodendritic level to regulate cell firing and secondarily enhance DA release. In addition, anatomical and indirect physiological data suggest the presence of NT receptors at the terminal level. However, a clear demonstration of the mechanism of action of NT on dopaminergic axon terminals is lacking. We hypothesize that NT acts to increase DA release by inhibiting the function of terminal D2 autoreceptors. To test this hypothesis, we used fast-scan cyclic voltammetry (FCV) to monitor in real time the axonal release of DA in the nucleus accumbens (NAcc). Results DA release was evoked by single electrical pulses and pulse trains (10 Hz, 30 pulses). Under these two stimulation conditions, we evaluated the characteristics of DA D2 autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D2 autoreceptors, quinpirole (1 μM), inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D2 receptor antagonist, sulpiride (5 μM), strongly enhanced DA release triggered by pulse trains, without any effect on DA release elicited by single pulses, thus confirming previous observations. We then determined the effect of NT (8–13) (100 nM) and found that although it failed to increase DA release evoked by single pulses, it strongly enhanced DA release evoked by pulse trains that lead to prolonged DA release and engage D2 autoreceptors. In addition, initial blockade of D2 autoreceptors by sulpiride considerably inhibited further facilitation of DA release generated by NT (8–13). Conclusion Taken together, these data suggest that NT enhances DA release principally by inhibiting the function of terminal D2 autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx.
机译：背景技术已知神经降压素（NT）在体树突状细胞水平上作用于多巴胺（DA）神经元，以调节细胞放电并继而增强DA的释放。另外，解剖学和间接生理学数据表明在末端水平存在NT受体。但是，缺乏NT对多巴胺能轴突末端的作用机理的明确证明。我们假设NT通过抑制末端D2自身受体的功能来增加DA的释放。为了验证这一假设，我们使用快速扫描循环伏安法（FCV）实时监测伏伏核（NAcc）中DA的轴突释放。结果DA释放是由单个电脉冲和脉冲序列（10 Hz，30个脉冲）引起的。在这两种刺激条件下，我们评估了DA D 2 自体受体的特征以及NT在NAcc壳和壳/核边界区域中NT的突触前作用。 D 2 自身受体的选择性激动剂喹吡罗（1μM）抑制单脉冲和训练脉冲引起的DA溢出。与之形成鲜明对比的是，选择性D 2 拮抗剂舒必利（5μM）大大增强了脉冲序列触发的DA释放，而对单脉冲引起的DA释放没有任何影响，从而证实了先前的观察结果。然后，我们确定了NT（8–13）（100 nM）的作用，发现尽管它不能增加单脉冲引起的DA释放，但它强烈增强了脉冲序列引起的DA释放，导致DA延长释放并参与D < sub> 2 自受体。此外，舒必利对D 2 自身受体的初步阻滞大大抑制了NT进一步促进DA释放（8-13）。结论总的来说，这些数据表明NT主要通过抑制末端D 2 自身受体的功能来增强DA的释放，而不是通过促进末端钙流入的更直接的机制来增强DA的释放。

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