Oxytocin Facilitates the Extinction of Conditioned Fear in Humans
Oxytocin Facilitates the Extinction of Conditioned Fear in Humans
复制标题
催产素有助于消除人类条件性恐惧
DOI：
10.1016/j.biopsych.2014.10.015
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发表时间：
2015-08-01
影响因子：
10.6
通讯作者：
Hurlemann, Rene
中科院分区：
文献类型：
--
作者：
Eckstein, Monika;Becker, Benjamin;Hurlemann, Rene
背景技术背景：目前焦虑症的神经回路模型包括在巴甫洛夫恐惧反应的获得过程中杏仁核中缺乏抑制性音调，以及杏仁核-内侧前额叶皮层回路中的消退反应编码不足。这两种反应之间的竞争往往导致恐惧的回归，限制了对焦虑的控制。然而，有一种假说认为，旨在减少杏仁核的活动，同时增强内侧前额叶皮质功能的药理学策略可以促进条件fear.METHODS的灭绝：杏仁核活动的内源性抑制剂中的关键是下丘脑肽催产素的社会恐惧信号。为了解决这个问题，催产素是否可以加强巴甫洛夫灭绝超越其控制社会恐惧的作用，我们进行了一项功能性磁共振成像实验，62名健康男性参与者在一个随机的，双盲的，平行组，安慰剂对照设计。具体而言，受试者暴露于巴甫洛夫恐惧条件反射范式之前，接受鼻内剂量（24 IU）的合成催产素或placebo.RESULTS：催产素，鼻内给药巴甫洛夫恐惧条件反射后，被发现增加皮肤电反应和前额叶皮质信号条件恐惧的早期阶段的灭绝和增强皮肤电导反应的下降在晚期阶段的灭绝。催产素还在这两个阶段引起对杏仁核反应的非特异性抑制。结论：总的来说，我们的研究结果确定催产素是参与巴甫洛夫灭绝的神经枢纽的差异作用调节剂。催产素作用的这种特定特征可能为增强焦虑症的预防性治疗开辟新的途径。
BACKGROUND: Current neurocircuitry models of anxiety disorders posit a lack of inhibitory tone in the amygdala during acquisition of Pavlovian fear responses and deficient encoding of extinction responses in amygdala-medial prefrontal cortex circuits. Competition between these two responses often results in a return of fear, limiting control over anxiety. However, one hypothesis holds that a pharmacologic strategy aimed at reducing amygdala activity while simultaneously augmenting medial prefrontal cortex function could facilitate the extinction of conditioned fear.METHODS: Key among the endogenous inhibitors of amygdala activity in response to social fear signals is the hypothalamic peptide oxytocin. To address the question whether oxytocin can strengthen Pavlovian extinction beyond its role in controlling social fear, we conducted a functional magnetic resonance imaging experiment with 62 healthy male participants in a randomized, double-blind, parallel-group, placebo-controlled design. Specifically, subjects were exposed to a Pavlovian fear conditioning paradigm before receiving an intranasal dose (24 IU) of synthetic oxytocin or placebo.RESULTS: Oxytocin, when administered intranasally after Pavlovian fear conditioning, was found to increase electrodermal responses and prefrontal cortex signals to conditioned fear in the early phase of extinction and to enhance the decline of skin conductance responses in the late phase of extinction. Oxytocin also evoked an unspecific inhibition of amygdalar responses in both phases.CONCLUSIONS: Collectively, our findings identify oxytocin as a differentially acting modulator of neural hubs involved in Pavlovian extinction. This specific profile of oxytocin action may open up new avenues for enhancing extinction-based therapies for anxiety disorders.