Peripheral effects of vagus nerve stimulation on anxiety and extinction of conditioned fear in rats.
Peripheral effects of vagus nerve stimulation on anxiety and extinction of conditioned fear in rats.
复制标题
迷走神经刺激对大鼠焦虑和条件性恐惧消除的外周影响。
DOI：
10.1101/lm.048447.118
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
McIntyre,ChristaK
中科院分区：
文献类型：
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作者：
Noble,LindseyJ;Chuah,Ashleigh;Callahan,KathleenK;Souza,RimenezR;McIntyre,ChristaK
迷走神经刺激（VNS）可增强大鼠条件性恐惧的消除。先前的研究结果支持这样的假设：VNS 对消退的影响是由于通过促进与消退相关的大脑通路的可塑性来增强消退记忆的巩固，然而，其他解释也是合理的。根据一种假设，迷走神经刺激可能会产生享乐效应，并通过反条件作用增强消退作用。根据另一种假设，迷走神经刺激可以减少暴露期间的焦虑，从而削弱条件刺激与厌恶性条件反应的关联。本组实验（1）使用条件性位置偏好（CPP）来识别与 VNS 相关的潜在奖励效应，（2）检查 VNS 对焦虑和消退增强的外周影响。雄性 Sprague-Dawley 大鼠通过手术在迷走神经周围植入袖带电极，并接受 CPP 任务，其中 VNS 和假刺激分别与两种不同环境中的一种配对，持续 5 天。在此过程之后，大鼠没有表现出位置偏好，这表明 VNS 没有奖励或厌恶。通过在 VNS 之前腹膜内给予甲基东莨菪碱来阻断外周毒蕈碱受体，检查外周副交感系统在 VNS 对高架十字迷宫的抗焦虑作用中的作用。甲基东莨菪碱可阻断 VNS 诱导的焦虑减少，但不会干扰 VNS 对条件性恐惧消退的增强，表明 VNS 的焦虑减少作用对于消退增强不是必需的。
Vagus nerve stimulation (VNS) enhances extinction of conditioned fear in rats. Previous findings support the hypothesis that VNS effects on extinction are due to enhanced consolidation of extinction memories through promotion of plasticity in extinction-related brain pathways however, alternative explanations are plausible. According to one hypothesis, VNS may produce a hedonic effect and enhance extinction through counter-conditioning. According to another hypothesis, VNS reduces anxiety during exposure and this weakens the association of conditioned stimuli with aversive conditioned responses. The present set of experiments (1) used conditioned place preference (CPP) to identify potential rewarding effects associated with VNS and (2) examined the peripheral effects of VNS on anxiety and extinction enhancement. Male Sprague–Dawley rats were surgically implanted with cuff electrodes around the vagus nerve and subjected to a CPP task in which VNS and sham stimulation were each paired with one of two distinct contexts over the course of 5 d. Following this procedure, rats did not show a place preference, suggesting that VNS is not rewarding or aversive. The role of the peripheral parasympathetic system in the anxiolytic effect of VNS on the elevated plus maze was examined by blocking peripheral muscarinic receptors with intraperitoneal administration of methyl scopolamine prior to VNS. Methyl scopolamine blocked the VNS-induced reduction in anxiety but did not interfere with VNS enhancement of extinction of conditioned fear, indicating that the anxiety-reducing effect of VNS is not necessary for the extinction enhancement.