Basolateral amygdala and stress-induced hyperexcitability affect motivated behaviors and addiction.
Basolateral amygdala and stress-induced hyperexcitability affect motivated behaviors and addiction.
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基底外侧杏仁核和压力引起的过度兴奋会影响动机行为和成瘾。
DOI：
10.1038/tp.2017.161
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发表时间：
2017-08-08
影响因子：
6.8
通讯作者：
Sharp BM
中科院分区：
文献类型：
--
作者：
Sharp BM
杏仁核整合和处理与奖励和恐惧、焦虑等情绪有关的信息，这些信息通过警告潜在的危险来促进生存。基底外侧杏仁核（BLA）与影响认知、动机和应激反应的脑区域双向通信，所述脑区域包括前额叶皮质、海马、丘脑核和触发去甲肾上腺素介导的应激反应的后脑区域。内源性杏仁核和BLA调节神经回路的破坏通常是由神经可塑性功能障碍引起的，通常是由于局部GABA能回路和主要多巴胺能输出神经元的分子改变。BLA兴奋性局部调节的变化是包括创伤后应激综合征（PTSD）、自闭症、注意力缺陷多动障碍（ADHD）和应激诱导的药物使用复发在内的障碍的行为障碍特征的基础。在这篇综述中，我们讨论了调节BLA/杏仁核及其主要输出神经元的生理和应激诱导功能障碍的分子机制和神经回路。我们认为，依赖于BLA的动机行为的压力的影响，这些行为包括吸毒和药物寻求，重点是尼古丁依赖性行为。在整个过程中，我们通过整合数十年的动物模型和人体试验成瘾研究，采取转化方法。我们表明，在动物成瘾模型中确定的BLA功能的变化，照亮人脑成像和行为研究更精确地描绘BLA机制。总而言之，BLA需要促进对自然奖励的反应并对二级药物条件暗示做出反应;恢复线索依赖性药物寻求;表达压力增强的尼古丁摄入量重新获取;并引发焦虑和恐惧。汇聚的证据表明，慢性应激导致BLA的主要输出神经元变得过度兴奋。
The amygdala integrates and processes incoming information pertinent to reward and to emotions such as fear and anxiety that promote survival by warning of potential danger. Basolateral amygdala (BLA) communicates bi-directionally with brain regions affecting cognition, motivation and stress responses including prefrontal cortex, hippocampus, nucleus accumbens and hindbrain regions that trigger norepinephrine-mediated stress responses. Disruption of intrinsic amygdala and BLA regulatory neurocircuits is often caused by dysfunctional neuroplasticity frequently due to molecular alterations in local GABAergic circuits and principal glutamatergic output neurons. Changes in local regulation of BLA excitability underlie behavioral disturbances characteristic of disorders including post-traumatic stress syndrome (PTSD), autism, attention-deficit hyperactivity disorder (ADHD) and stress-induced relapse to drug use. In this Review, we discuss molecular mechanisms and neural circuits that regulate physiological and stress-induced dysfunction of BLA/amygdala and its principal output neurons. We consider effects of stress on motivated behaviors that depend on BLA; these include drug taking and drug seeking, with emphasis on nicotine-dependent behaviors. Throughout, we take a translational approach by integrating decades of addiction research on animal models and human trials. We show that changes in BLA function identified in animal addiction models illuminate human brain imaging and behavioral studies by more precisely delineating BLA mechanisms. In summary, BLA is required to promote responding for natural reward and respond to second-order drug-conditioned cues; reinstate cue-dependent drug seeking; express stress-enhanced reacquisition of nicotine intake; and drive anxiety and fear. Converging evidence indicates that chronic stress causes BLA principal output neurons to become hyperexcitable.
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