Presynaptic action of neurotensin on dopamine release through inhibition of D2 receptor function
Presynaptic action of neurotensin on dopamine release through inhibition of D2 receptor function
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DOI：
10.1186/1471-2202-10-96
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发表时间：
2009-08-14
期刊：
影响因子：
2.4
通讯作者：
Trudeau, Louis-Eric
中科院分区：
文献类型：
--
作者：
Fawaz, Charbel S.;Martel, Philippe;Trudeau, Louis-Eric
背景资料：神经降压素（NT）在体树突水平作用于多巴胺（DA）神经元，调节细胞放电并促进DA释放。此外，解剖学和间接生理数据表明，在终端水平的NT受体的存在。然而，NT对多巴胺能轴突终末的作用机制尚缺乏明确的证据。我们假设NT通过抑制末端D2自受体的功能来增加DA的释放。为了验证这一假设，我们采用快速扫描循环伏安法（FCV）对中脑背外侧核（NAcc）内DA的轴突释放进行了真实的实时监测。在这两种刺激条件下，我们评估了DA D-2自身受体的特性和NT在NAcc壳和壳/核边界区域的突触前作用。选择性D-2自身受体激动剂，quinpirole（1 μ M），抑制DA溢出诱发的单脉冲和火车。与此形成鲜明对比的是，选择性的D-2受体拮抗剂，舒必利（5 μ M），强烈增强DA释放触发脉冲串，没有任何影响DA释放引起的单脉冲，从而证实了以前的观察。然后，我们确定了NT（8-13）（100 nM）的作用，并发现尽管它未能增加由单脉冲诱发的DA释放，但它强烈增强了由脉冲串诱发的DA释放，导致延长的DA释放并接合D-2自身受体。此外，舒必利对D-2自身受体的初始阻断显著抑制了NT对DA释放的进一步促进作用（8-13）。结论：综上所述，这些数据表明NT主要通过抑制末端D-2自身受体的功能而不是通过更直接的机制如促进末端钙内流来促进DA释放。
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 D-2 autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D-2 autoreceptors, quinpirole (1 mu M), inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D-2 receptor antagonist, sulpiride (5 mu M), 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 D-2 autoreceptors. In addition, initial blockade of D-2 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 D-2 autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx.