Functional interactions between dopamine, serotonin and norepinephrine neurons: an in-vivo electrophysiological study in rats with monoaminergic lesions
Functional interactions between dopamine, serotonin and norepinephrine neurons: an in-vivo electrophysiological study in rats with monoaminergic lesions
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DOI：
10.1017/s1461145707008383
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发表时间：
2008-08-01
影响因子：
4.8
通讯作者：
Blier, Pierre
中科院分区：
文献类型：
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作者：
Guiard, Bruno P.;El Mansari, Mostafa;Blier, Pierre
解剖学研究已经证实大脑中主要的单胺、血清素 (5-HT)、去甲肾上腺素 (NE) 和多巴胺 (DA) 神经元之间存在相互关系。因此，本研究旨在检查 DA 耗尽的大鼠中 5-HT 和 NE 神经元的放电活性，以及 5-HT 或 NE 耗尽的大鼠中 DA 神经元的放电活性。 6-羟基多巴胺（6-OHDA）引起的 DA 神经元的选择性损伤使中缝背核（DR）5-HT 神经元的自发放电活性降低了 60%，从而揭示了 DA 输入对这些 5-HT 神经元的兴奋作用。相比之下，5,7-二羟色胺（5,7-DHT）产生的5-HT神经元的选择性损伤使VTA DA神经元的放电活性增强了36%，从而表明5-HT输入对这些DA神经元的抑制作用。关于 DA 和 NE 神经元之间的相互作用，观察到通过腹侧被盖区 (VTA) 注射 6-OHDA 实现 DA 神经元的选择性损失，使蓝斑 (LC) NE 神经元子集的放电活动增加 47%。 LC 内注射 6-OHDA 后选择性丧失 NE 神经元，使 VTA DA 神经元的放电活性增强了 70%，这表明 NE 输入对 VTA DA 神经元具有净抑制作用。这些发现对于旨在同时增强 5-HT、NE 和 DA 传输的抗抑郁治疗具有重要影响。事实上，基于对这种相互作用的理解，有可能制定策略，通过防止适得其反的负反馈行为来提高抗抑郁药物的有效性。
Anatomical studies have established the existence of reciprocal relationships between the main population of monoamine, serotonin (5-HT), norepinephrine (NE) and dopamine (DA) neurons in the brain. The present study was thus conducted to examine the firing activity of 5-HT and NE neurons in DA-depleted rats, as well as the firing activity of DA neurons in 5-HT- or NE-depleted rats. The selective lesion of DA neurons elicited by 6-hydroxydopamine (6-OHDA) decreased the spontaneous firing activity of dorsal raphe (DR) nucleus 5-HT neurons by 60%, thus revealing the excitatory effect of the DA input on these 5-HT neurons. In contrast, the selective lesion of 5-HT neurons produced by 5,7-dihydroxytryptamine (5,7-DHT) enhanced by 36% the firing activity of VTA DA neurons, thereby indicating an inhibitory effect of the 5-HT input on these DA neurons. With regard to the reciprocal interaction between DA and NE neurons, it was observed that the selective loss of DA neurons achieved by the intra-ventral tegmental area (VTA) injection of 6-OHDA increased the firing activity of a subset of locus coeruleus (LC) NE neurons by 47%. The selective loss of NE neurons in response to the intra-LC injection of 6-OHDA enhanced the firing activity of VTA DA neurons by 70%, demonstrating a net inhibitory role of the NE input on VTA DA neurons. These findings have important consequences for antidepressant treatments aimed at enhancing simultaneously 5-HT, NE and DA transmission. Indeed, based on the understanding of such interactions, it may be possible to develop strategies to improve the effectiveness of antidepressant drugs by preventing counter-productive negative feedback actions.