Electrophysiological and neurochemical effects of long-term vagus nerve stimulation on the rat monoaminergic systems
Electrophysiological and neurochemical effects of long-term vagus nerve stimulation on the rat monoaminergic systems
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DOI：
10.1017/s1461145712000387
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发表时间：
2013-03-01
影响因子：
4.8
通讯作者：
Blier, Pierre
中科院分区：
文献类型：
--
作者：
Manta, Stella;El Mansari, Mostafa;Blier, Pierre
迷走神经刺激（VNS）是治疗难治性癫痫和抑郁症的有效方法。大鼠脑中的电生理记录已经表明，慢性VNS增加去甲肾上腺素（NE）神经元的放电活动，随后通过激活其兴奋性α（1）-肾上腺素受体增加5-羟色胺（5-HT）神经元的放电活动。长期VNS显示增加海马中突触后5-HT 1A受体的紧张性激活。本研究旨在研究VNS对不同脑区细胞外5-HT，NE和多巴胺（DA）水平的影响，使用在体微透析，在海马中NE的传输，和DA神经元放电活动的电生理学。大鼠被植入VNS装置，并用治疗抵抗性抑郁症中使用的标准参数（0.25 mA，20 Hz，500 ms，30 s on-5 min off）刺激14 d。本研究结果显示，2周VNS显著增加前额叶皮层和海马细胞外NE水平，并增强锥体神经元突触后α（2）-肾上腺素受体的紧张性激活。电生理实验显示，腹侧被盖区DA神经元放电率显着下降后，长期VNS;细胞外DA水平，但在前额叶皮层和背外侧核增加。慢性迷走神经刺激可显著增加中缝背核细胞外5-HT水平，但海马和前额叶皮质细胞外5-HT水平无明显变化。总之，VNS在增加单胺能系统在治疗难治性抑郁症的目标传输的影响，应参与，至少部分，在其抗抑郁药的性质观察到的患者没有响应许多抗抑郁药的策略。
Vagus nerve stimulation (VNS) is an adjunctive treatment for resistant epilepsy and depression. Electrophysiological recordings in the rat brain have already shown that chronic VNS increases norepinephrine (NE) neuronal firing activity and, subsequently, that of serotonin (5-HT) neurons through an activation of their excitatory alpha(1)-adrenoceptors. Long-term VNS was shown to increase the tonic activation of post-synaptic 5-HT1A receptors in the hippocampus. This study was aimed at examining the effect of VNS on extracellular 5-HT, NE and dopamine (DA) levels in different brain areas using in vivo microdialysis, on NE transmission in the hippocampus, and DA neuronal firing activity using electrophysiology. Rats were implanted with a VNS device and stimulated for 14 d with standard parameters used in treatment-resistant depression (0.25 mA, 20 Hz, 500 ms, 30 s on-5 min off). The results of the present study revealed that 2-wk VNS significantly increased extracellular NE levels in the prefrontal cortex and the hippocampus and enhanced the tonic activation of post-synaptic alpha(2)-adrenoceptors on pyramidal neurons. The electrophysiological experiments revealed a significant decrease in ventral tegmental area DA neuronal firing rate after long-term VNS; extracellular DA levels were nevertheless increased in the prefrontal cortex and nucleus accumbens. Chronic VNS significantly increased extracellular 5-HT levels in the dorsal raphe but not in the hippocampus and prefrontal cortex. In conclusion, the effect of VNS in increasing the transmission of monoaminergic systems targeted in the treatment of resistant depression should be involved, at least in part, in its antidepressant properties observed in patients not responding to many antidepressant strategies.