Alcohol action on extended amygdala glutamate synapses

酒精对延长杏仁核谷氨酸突触的作用

基本信息

批准号：
10670471
负责人：
DANNY G WINDER
金额：
$ 6.65万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10670471
关键词：
Ablation Abstinence Acute Adrenergic Receptor Affective Alcohol consumption Alcohol dehydrogenase Alcohol dependence Alcohol withdrawal syndrome Alcoholism Alcohols Amygdaloid structure Antidepressive Agents Anxiety Behavior Behavioral Cell Nucleus Chronic Corticotropin-Releasing Hormone Receptors Data Development Down-Regulation Ethanol Ethanol dependence Family history of Financial Hardship Funding Glutamates Health Human Ketamine Knockout Mice Literature Long-Term Depression Long-Term Potentiation Maps Masks Mediating Mental Depression Messenger RNA Modeling Mus N-Methyl-D-Aspartate Receptors NMDA receptor antagonist Negative Reinforcements Neurons Neuropeptides Play Procedures Process Pyrazoles Receptor Signaling Regulation Reporter Rewards Role Series Signal Transduction Societies Stress Structure of terminal stria nuclei of preoptic region Synapses System Testing Up-Regulation affective disturbance alcohol abstinence alcohol exposure alcohol sensitivity alcohol use disorder base behavioral outcome behavioral response brain circuitry depressive behavior diphtheria toxin receptor drinking drinking behavior drug action experimental study glutamatergic signaling inhibitor new therapeutic target postsynaptic public health relevance receptor receptor function receptor-mediated signaling therapeutic development transmission process

项目摘要

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.

描述（适用提供）：酒精中毒是我们社会的巨大健康和经济燃烧。越来越多的文献表明，扩展的杏仁核在应力奖励相互作用中起关键作用，这可能介导了对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会调节CRF受体依赖的谷氨酸释放的增强，以及突触后NMDA，我们提出了一系列实验，以绘制CRF受体信号传导调节谷氨酸突触的机制，以探索NMDA受体的变化，并探索了该物品的变化。我们进一步建议探索这些过程破坏对饮酒诱发抑郁行为的影响。