Serotonergic and Noradrenergic Pathways Are Required for the Anxiolytic-like and Antidepressant-like Behavioral Effects of Repeated Vagal Nerve Stimulation in Rats
Serotonergic and Noradrenergic Pathways Are Required for the Anxiolytic-like and Antidepressant-like Behavioral Effects of Repeated Vagal Nerve Stimulation in Rats
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DOI：
10.1016/j.biopsych.2011.07.020
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发表时间：
2011-11-15
影响因子：
10.6
通讯作者：
Frazer, Alan
中科院分区：
文献类型：
--
作者：
Furmaga, Havan;Shah, Aparna;Frazer, Alan
背景资料：迷走神经刺激（VNS）是用于治疗难治性抑郁症，但很少有临床前的研究，其影响时，随着时间的推移，反复使用临床相关的刺激参数在nonanesthesious.Methods：新奇抑制喂养试验（NSFT）和强迫游泳试验（FST）被用来评估的抗焦虑和抗抑郁样电位的VNS在大鼠，分别。VNS的行为效应与通过渗透微泵给药的地昔帕明（10 mg/kg/d）和舍曲林（7.5mg/kg/d）进行了比较。这些实验是在完整的大鼠以及那些有选择性的破坏，无论是在大脑中的5-羟色胺（5，7-DHT），或6-羟多巴胺（6-OHDA.Results）的神经毒素，5，7-二羟色胺（5，7-DHT），或6-羟多巴胺（6-OHDA.Results）引起的5-羟色胺或去甲肾上腺素能神经元在NSFT重复给药的VNS，多巴胺，舍曲林减少潜伏期喂养。在FST中，重复VNS，VNS和舍曲林引起的不动性降低; VNS引起的不动性降低是由于游泳和攀爬行为的增加。用5，7-DHT处理的大鼠，VNS和舍曲林的作用被消除，但不包括VNS在NSFT和FST中的作用。在6-OHDA处理的大鼠中，在两种行为测试中，舍曲林的作用被消除，但舍曲林的作用没有被消除。在6-OHDA处理的大鼠中，VNS对FST中不动和攀爬的作用没有被阻断。有没有显着差异所造成的任何治疗或由insulines.Conclusions：血清素能神经所需的反复VNS诱导的抗焦虑和抗抑郁样作用的自发活动。去甲肾上腺素能神经也可以被VNS激活，从而引起其抗焦虑样作用。
Background: Vagal nerve stimulation (VNS) is used for treatment-refractory depression, but there are few preclinical studies of its effects when administered repeatedly over time using clinically relevant stimulation parameters in nonanesthetized animals.Methods: The novelty-suppressed feeding test (NSFT) and forced swim test (FST) were used to evaluate the anxiolytic- and antidepressant-like potential of VNS in rats, respectively. The behavioral effects of VNS were compared with those of desipramine (DMI; 10 mg/kg/day) and sertraline (7.5 mg/kg/day) administered via osmotic minipump. Such experiments were carried out in intact rats as well as those that had selective destruction of either serotonin or noradrenergic neurons in brain caused by the neurotoxins, 5,7-dihyroxytryptamine (5,7-DHT), or 6-hydroxydopamine (6-OHDA).Results: Repeated administration of VNS, DMI, and sertraline decreased latency to feed in the NSFT. In the FST, repeated VNS, DMI, and sertraline caused decreased immobility; the VNS-induced decrease in immobility resulted from increases in both swimming and climbing behaviors. Effects of VNS and sertraline, but not DMI, in both the NSFT and the FST were abolished in rats treated with 5,7-DHT. Effects of DMI in both behavioral tests, but not those of sertraline, were abolished in 6-OHDA treated rats. VNS effects on immobility and climbing in the FST were not blocked in the 6-OHDA-treated rats. There was no significant difference in locomotor activity caused by any of the treatments or by the lesions.Conclusions: Serotonergic nerves are required for repeated VNS-induced anxiolytic- and antidepressant-like effects. Noradrenergic nerves can also be activated by VNS to cause its anxiolytic-like effect.