Inhibition of amygdaloid dopamine D2 receptors impairs emotional learning measured with fear-potentiated startle
Inhibition of amygdaloid dopamine D2 receptors impairs emotional learning measured with fear-potentiated startle
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DOI：
10.1016/s0006-8993(01)02243-0
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发表时间：
2001-04-27
期刊：
影响因子：
2.9
通讯作者：
Kokkinidis, L
中科院分区：
文献类型：
--
作者：
Greba, Q;Gifkins, A;Kokkinidis, L
在了解巴甫洛夫条件性恐惧反应的获得和表达背后的神经回路方面已经取得了相当大的进展。在介导恐惧的复杂细胞和分子过程中，杏仁体多巴胺（DA），起源于中脑腹侧被盖区（VTA）的细胞，被认为有助于恐惧动机的反应。考虑到DA D-2受体的阻断是抗精神病药物的常见作用机制，Eve假设杏仁核中D-2受体的抑制可能与这些药物的抗偏执作用有关。为了评估杏仁体DA D-2受体在厌恶情绪中的作用，在巴甫洛夫恐惧条件反射之前将D-2受体拮抗剂雷氯必利注入杏仁体。强化惊吓被用作恐惧和焦虑的行为指标。经典的恐惧条件反射和声学惊吓测试进行了一个单一的会议，允许伴随评估休克反应性与惊吓增强。根据剂量的不同，研究结果发现，在杏仁核中注射雷氯必利后，条件性恐惧的获得和保持会受到损害。此外，学习障碍与电击检测和恐惧表达无关，用声惊吓的电击敏感性进行评估。这些发现进一步完善了杏仁核为基础的情绪学习和记忆的已知神经机制，并被解释为表明，沿着D-1受体，杏仁核中的D-2受体可能介导新获得的恐惧联想的形成和保持。(C)2001 Elsevier science B. V.保留所有权利。
Considerable advances have been made in understanding the neurocircuitry underlying the acquisition and expression of Pavlovian conditioned fear responses. Within the complex cellular and molecular processes mediating fearfulness, amygdaloid dopamine (DA), originating from cells in the ventral tegmental area (VTA) of the midbrain, is thought to contribute to fear-motivated responding. Considering that blockade of DA D-2 receptors is a common mechanism of action for antipsychotic agents, eve hypothesized that inhibition of D-2 receptors in the amygdala may be involved in the antiparanoid effects of these drugs. To assess the role of amygdaloid DA D-2 receptors in aversive emotionality, the D-2 receptor antagonist raclopride was infused into the amygdala prior to Pavlovian fear conditioning. Potentiated startle was used as a behavioral indicator of fear and anxiety. Classical fear conditioning and acoustic startle testing were conducted in a single session allowing for the concomitant assessment of shock reactivity with startle enhancement. Depending on dose, the results found conditioned fear acquisition and retention to be impaired following administration of raclopride into the amygdala. Additionally, the learning deficit was dissociated from shock detection and from fear expression assessed with the shock sensitization of acoustic startle. These findings further refine the known neural mechanisms of amygdala-based emotional learning and memory and were interpreted to suggest that, along with D-1 receptors, D-2 receptors in the amygdala may mediate the formation and the retention of newly-acquired fear associations. (C) 2001 Elsevier science B.V. All rights reserved.