Effects of chronic ethanol withdrawal on the amygdala

描述(申请人提供)：影响酗酒者继续酗酒的一个重要因素是戒酒过程中经历的严重焦虑。支配焦虑这些长期变化的神经生物学机制目前尚不清楚。在大脑中，杏仁核是一个主要的情感中心，调节着习得性恐惧和焦虑的表达。我们实验室的初步数据表明，慢性酒精和戒断后，杏仁外侧核/杏仁基底外侧核(BLA)突触的谷氨酸能传递发生了变化。谷氨酸受体，特别是AMPA型和潜在的海藻酸型受体(Li等人，2001)，在杏仁核内的长期突触改变中发挥着重要作用。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焦虑效应有关。目前的应用将解决核心假设，即长期戒酒将以类似于恐惧学习的方式，以不同方式改变AMPA和海人藻酸介导的EC/BLA突触的谷氨酸能传递。

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.