Alcohol action on extended amygdala glutamate synapses

 描述（由申请人提供）：酗酒是一个巨大的健康和经济负担，对我们的社会。越来越多的文献表明，扩展杏仁核在压力-奖励相互作用中起着关键作用，可能介导慢性酒精暴露的关键行为反应。我们证明，慢性间歇性酒精暴露上调CRF受体依赖的谷氨酸释放增强，以及突触后NMDA受体功能在延长杏仁核谷氨酸突触。我们建议在这里测试一个“两击”模型，即慢性酒精暴露和戒断所产生的情感中断依赖于扩展杏仁核谷氨酸突触的协调前和突触后调节。我们提出了一系列的实验，以绘制出CRF受体信号调节谷氨酸突触的机制，并探讨与酒精暴露和戒断发生的NMDA受体功能的改变。我们进一步建议探讨这些过程的中断对酒精戒断引起的抑郁行为的影响。

 DESCRIPTION (provided by applicant): Alcoholism is a tremendous health and financial burden on our society. A growing literature indicates that the extended amygdala plays a key role in stress-reward interactions that may mediate key behavioral responses to chronic alcohol exposure. We demonstrated that chronic intermittent alcohol exposure up regulates CRF receptor dependent augmentation of glutamate release, as well as postsynaptic NMDA receptor function at extended amygdala glutamate synapses. We propose here to test a "two-hit" model, whereby affective disruptions produced by chronic alcohol exposure and withdrawal depend upon the coordinated pre- and postsynaptic regulation of extended amygdala glutamate synapses. We propose a series of experiments to map out mechanisms by which CRF receptor signaling regulates glutamate synapses, and to explore the alterations in NMDA receptor function that occur with alcohol exposure and withdrawal. We further propose to explore the impact of disruption of these processes on alcohol-abstinence induced depressive behaviors.