Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission
Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission
复制标题
DOI：
10.1124/jpet.106.104166
复制
发表时间：
2006-08-01
影响因子：
3.5
通讯作者：
Debonnel, Guy
中科院分区：
文献类型：
--
作者：
Dorr, Adrienne E.;Debonnel, Guy
迷走神经刺激（VNS）是一种抗癫痫治疗，最近显示出作为抗抑郁药的前景。然而，其抗抑郁作用机制尚不清楚。5-羟色胺（5-HT，serotonergic）和去甲肾上腺素（norepinephrine，NE）系统参与抑郁症的病理生理学和抗抑郁药的作用机制。本研究分析了5-HT和NE神经元的放电率在他们的脑干核：中缝背核（DRN）和蓝斑（LC），分别。长期VNS治疗后，DRN和LC的基础放电频率显著增加。短期VNS治疗后，放电率显着较高的LC（在1小时和3天）。由于其放电率的变化可能是由于自身受体敏感性的改变，因此评估了自身受体对其各自激动剂急性给药的反应。然而，在DRN中没有观察到显著差异。5-HT 1A体树突和α 2-肾上腺素能自身受体的剂量反应曲线在长期VNS和对照组之间没有显著差异。迷走神经刺激似乎有一种新的抗抑郁作用机制，使其在难治性抑郁症中有效。LC的放电频率显著早于DRN的基础放电。由于LC对DRN具有兴奋性影响，因此增加的DRN放电速率可能继发于来自VNS的初始增加的LC放电速率。
Vagus nerve stimulation (VNS) is an antiepileptic treatment, which has recently shown promise as an antidepressant. Yet, its antidepressant mechanisms of action are unknown. Serotonergic [5-hydroxytryptamine (5-HT, serotonin)] and noradrenergic [norepinephrine ( NE)] systems are involved in the pathophysiology of depression and in the mechanisms of action of antidepressants. The present study analyzes 5-HT and NE neuronal firing rates in their brainstem nuclei: the dorsal raphe nucleus (DRN) and locus coeruleus (LC), respectively. The basal firing rates in the DRN and LC were significantly increased after long-term treatments with VNS. After short-term VNS treatments, firing rates were significantly higher for LC (at 1 h and 3 days). As changes in their firing rate may have been due to altered autoreceptor sensitivities, the responses of autoreceptors to the acute administration of their respective agonists were assessed. However, no significant difference was seen in the DRN. No significant differences in dose response curves for 5-HT1A somatodendritic and alpha(2)-adrenergic autoreceptors were noticed between long-term VNS and controls. VNS appears to have a novel mechanism of antidepressant action, enabling its effectiveness in treatment-resistant depression. LC firing rates significantly increase earlier than the DRN basal firing. As the LC has an excitatory influence on DRN, it is possible that the increased DRN firing rate is secondary to an initial increased LC firing rate from VNS.