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：
8658782
负责人：
DANNY G WINDER
金额：
$ 34.54万
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：
2010-07-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8658782
关键词：
Acute Adaptive Behaviors Agonist Alcohol abuse Alcohol consumption Alcohol withdrawal syndrome Alcoholism Alcohols Amygdaloid structure Anatomy Anxiety Behavior Brain Brain region Cell Nucleus Characteristics Chronic Complex Corticotropin-Releasing Hormone Receptors Data Dependence Development Diffuse Dopamine Environment Ethanol Fright Genetic Glutamates Health Individual Kindling (Neurology)Knock-out Knockout Mice Literature Long-Term Potentiation Maintenance Midbrain structure Molecular Mus N-Methyl-D-Aspartate Receptors Nature Neurons Participant Pituitary Gland Play Process Property Receptor Signaling Recruitment Activity Research Personnel Rewards Role Series Signal Transduction Signaling Molecule Societies Stimulus Stress Structure of terminal stria nuclei of preoptic region Synapses Synaptic plasticity System Testing Treatment Protocols Viral Work addiction alcohol abuse therapy alcohol behavior alcohol effect alcohol exposure alcohol sensitivity drinking drinking behavior extracellular insight neuroadaptation receptor function research study response species difference stem stressor therapeutic development tool 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 a series of interconnected brain regions referred to as the extended amygdala plays a key role in alcohol-related behaviors. In isolated studies, we and others have identified adaptations that occur at synapses in these regions in response to acute and chronic ethanol exposure. Here, we propose experiments to in parallel examine key points in this circuitry for their responses to a common alcohol treatment regimen, to better determine the concerted effects of ethanol and ethanol withdrawal. Moreover, we will assess molecular mechanisms involved in these actions through the use of a new conditional knockout mouse for the NMDA receptor subunit NR2B combined with a viral-directed knockout strategy. In total, the proposed work will begin to define specific mechanisms likely to play key roles in pathological adaptations and behaviors associated with chronic alcohol intake, thus providing new potential opportunities for therapeutic development.

描述（由申请人提供）：酒精中毒是我们社会的巨大健康和经济负担。越来越多的文献表明，一系列被称为扩展杏仁核的大脑区域在与酒精相关的行为中起关键作用。在孤立的研究中，我们和其他人确定了响应急性和慢性乙醇暴露的突触中发生的适应性。在这里，我们建议在该电路中并行检查其对常见酒精治疗方案的反应中的关键点，以更好地确定乙醇和乙醇提取的协同作用。此外，我们将通过将新的条件基因敲除小鼠用于NMDA受体亚基NR2B与病毒定向的敲除策略相结合的新条件敲除小鼠来评估这些作用中涉及的分子机制。总的来说，拟议的工作将开始定义可能在与慢性酒精摄入相关的病理适应和行为中起关键作用的特定机制，从而为治疗性发育提供了新的潜在机会。