去甲肾上腺素对大鼠蓝斑刺激诱发的多巴胺传递的调制。
Noradrenergic Modulation of Dopamine Transmission Evoked by Electrical Stimulation of the Locus Coeruleus in the Rat Brain.
机构信息
Department of Biotechnical and Clinical Laboratory Sciences and ‡Neuroscience Program, University at Buffalo, State University of New York , Buffalo, New York 14214-3005, United States.
出版信息
ACS Chem Neurosci. 2017 Sep 20;8(9):1913-1924. doi: 10.1021/acschemneuro.7b00078. Epub 2017 Jun 21.
Central norepinephrine (NE) and dopamine (DA) are involved in a variety of physiological functions and behaviors. Accumulating evidence suggests that NE neurons originating from the locus coeruleus (LC) innervate DA neurons of the ventral tegmental area (VTA) and influence VTA-DA neural activity. However, the underlying mechanisms of how LC-NE regulates DA transmission via VTA-DA neurons remain largely unexplored. Herein, we investigated how electrical stimulation of the LC modulates VTA-DA neurotransmission in the nucleus accumbens (NAc). For this study, catecholamine release in the NAc and VTA evoked by electrical stimulation of the LC in urethane-anesthetized rats was simultaneously monitored with carbon-fiber microelectrodes using in vivo multichannel fast-scan cyclic voltammetry for comparison of its extracellular regulation. Pharmacological, anatomical, and electrochemical evidence suggest that electrical stimulation of the LC evokes NE release in the VTA and activates VTA-DA neurons, resulting in DA release in the NAc. The electrically evoked DA in the NAc was regulated by D2 receptors and DA transporters (DAT) as well as α-adrenergic receptors in the VTA, whereas NE release in the VTA was regulated by α-adrenergic receptors and NE transporters (NET) not by D2 receptors or DAT. These results suggest that electrical stimulation of LC modulates VTA-DA neurons and DA transmission in the NAc via NE receptors.
中枢去甲肾上腺素（NE）和多巴胺（DA）参与多种生理功能和行为。越来越多的证据表明，起源于蓝斑核（LC）的 NE 神经元支配腹侧被盖区（VTA）的 DA 神经元，并影响 VTA-DA 神经活动。然而，LC-NE 通过 VTA-DA 神经元调节 DA 传递的潜在机制在很大程度上仍未得到探索。在此，我们研究了 LC 电刺激如何调节伏隔核（NAc）中的 VTA-DA 神经传递。在这项研究中，我们使用体内多通道快速扫描循环伏安法，同时用碳纤维微电极监测在乌拉坦麻醉大鼠中 LC 电刺激引起的 NAc 和 VTA 中的儿茶酚胺释放，以比较其细胞外调节。药理学、解剖学和电化学证据表明，LC 电刺激会引发 VTA 中的 NE 释放并激活 VTA-DA 神经元，从而导致 NAc 中的 DA 释放。NAc 中电诱发的 DA 受到 VTA 中的 D2 受体和 DA 转运体（DAT）以及 α-肾上腺素能受体的调节，而 VTA 中的 NE 释放则受到 α-肾上腺素能受体和 NE 转运体（NET）的调节，而不受 D2 受体或 DAT 的调节。这些结果表明，LC 电刺激通过 NE 受体调节 VTA-DA 神经元和 NAc 中的 DA 传递。
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