Effects of chronic ethanol withdrawal on the amygdala

描述（由申请人提供）： 影响酗酒者继续滥用酒精的一个重要因素是在戒断期间经历的严重焦虑。目前还不清楚控制这些长期焦虑变化的神经生物学机制。在大脑中，杏仁核是主要的情绪中心，调节习得性恐惧和焦虑的表达。我们实验室的初步数据表明，在慢性乙醇和戒断的情况下，外侧杏仁核/基底外侧杏仁核（BLA）突触中的多巴胺能传递发生了变化。谷氨酸受体，特别是AMPA型和潜在的海人藻酸盐型受体（Li等人，2001），在杏仁核内的长期突触改变中起主要作用。然而，我们不知道这些受体是否与外囊（EC）/BLA突触中酒精戒断的长期致焦虑作用有关。本申请将解决的中心假设，从慢性乙醇退出将差异改变AMPA和红藻氨酸介导的多巴胺能传递在EC/BLA突触的方式类似于恐惧学习。

DESCRIPTION (provided by applicant): A significant factor that influences alcoholics to continue to abuse alcohol is the severe anxiety experienced during withdrawal. The neurobiological mechanisms governing these long-lasting alterations in anxiety are currently unknown. Within the brain, the amygdala is a major emotional epicenter and regulates the expression of both learned-fear and anxiety. Preliminary data from our lab has shown that there are changes in glutamatergic transmission in the lateral amygdala/basolateral amygdala (BLA) synapses with chronic ethanol and withdrawal. Glutamate receptors, particularly AMPA-type and potentially kainite-type receptors (Li et al., 2001), play a major role in long-term synaptic alterations within the amygdala. However, we do not know if these receptors are associated with the long-term anxiogenic effects of alcohol withdrawal in the external capsule (EC)/BLA synapses. The current application will address the central hypothesis that withdrawal from chronic ethanol will differentially alter AMPA- and kainate-mediated glutamatergic transmission at EC/BLA synapses in a manner similar to fear learning.