Understanding the role of dopamine in conditioned and unconditioned fear
Understanding the role of dopamine in conditioned and unconditioned fear
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DOI：
10.1515/revneuro-2018-0023
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发表时间：
2019-04-01
影响因子：
4.1
通讯作者：
Coimbra, Norberto C.
中科院分区：
文献类型：
--
作者：
Brandao, Marcus L.;Coimbra, Norberto C.
焦虑症的药理学和分子成像研究主要集中在5-羟色胺系统。与此同时，60年来，多巴胺一直被认为是奖赏的神经递质，特别是因为它在中皮质边缘系统的神经末梢发挥作用。最近，人们对多巴胺在众所周知的大脑厌恶系统中的中介作用越来越感兴趣，特别是考虑到最近获得的关于D-2多巴胺受体在无条件恐惧中的作用的证据。然而，已经证实，来自腹侧被盖区(VTA)的多巴胺(DA)能神经元对中皮质边缘通路的兴奋与焦虑的发生有关。在这条通路所支配的前脑区域中，杏仁核是条件性恐惧神经回路的重要组成部分。目前的发现表明，连接VTA和杏仁基底外侧核的多巴胺D-2受体信号通路调节恐惧和焦虑，而中脑顶盖的神经回路是先天恐惧表达的基础。这些DA神经元投射到脑厌恶系统的尾侧结构，其A13核被认为是这些神经元的起源。在这篇文章中，我们回顾了研究中获得的数据，这些数据表明DA受体介导的上行或下行DA通路机制在恐惧/焦虑过程中扮演着相反的角色。多巴胺似乎通过在大脑吻部水平起作用来调节条件性恐惧，并在大脑中部水平调节无条件恐惧。
Pharmacological and molecular imaging studies in anxiety disorders have primarily focused on the serotonin system. In the meantime, dopamine has been known as the neurotransmitter of reward for 60 years, particularly for its action in the nervous terminals of the mesocorticolimbic system. Interest in the mediation by dopamine of the well-known brain aversion system has grown recently, particularly given recent evidence obtained on the role of D-2 dopamine receptors in unconditioned fear. However, it has been established that excitation of the mesocorticolimbic pathway, originating from dopaminergic (DA) neurons from the ventral tegmental area (VTA), is relevant for the development of anxiety. Among the forebrain regions innervated by this pathway, the amygdala is an essential component of the neural circuitry of conditioned fear. Current findings indicate that the dopamine D-2 receptor-signaling pathway connecting the VTA to the basolateral amygdala modulates fear and anxiety, whereas neural circuits in the midbrain tectum underlie the expression of innate fear. The A13 nucleus of the zona incerta is proposed as the origin of these DA neurons projecting to caudal structures of the brain aversion system. In this article we review data obtained in studies showing that DA receptor-mediated mechanisms on ascending or descending DA pathways play opposing roles in fear/anxiety processes. Dopamine appears to mediate conditioned fear by acting at rostral levels of the brain and regulate unconditioned fear at the mid brain level.