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：
10886286
负责人：
DANNY G WINDER
金额：
$ 3.32万
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/10886286
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 Synaptic plasticity System Testing Up-Regulation affective disturbance alcohol abstinence alcohol exposure alcohol sensitivity alcohol use disorder 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 presynaptic public health relevance receptor receptor function receptor-mediated signaling success 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（由申请人提供）：酗酒给我们的社会带来了巨大的健康和经济负担。越来越多的文献表明，扩展的杏仁核在压力-奖励相互作用中发挥着关键作用，可能介导对慢性酒精暴露的关键行为反应。慢性间歇性酒精暴露上调 CRF 受体依赖性谷氨酸释放增强，以及扩展杏仁核谷氨酸突触的突触后 NMDA 受体功能。 “二次打击”模型，因此慢性酒精暴露和戒断产生的情感破坏取决于扩展杏仁核谷氨酸突触的突触前和突触后协调调节，我们提出了一系列实验来找出 CRF 受体信号传导调节谷氨酸的机制。我们进一步建议探索这些过程的破坏对戒酒引起的抑郁症的影响。行为。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Driving the Downward Spiral: Alcohol-Induced Dysregulation of Extended Amygdala Circuits and Negative Affect.

推动向下螺旋：酒精引起的杏仁核环路扩展失调和负面影响。

DOI：
发表时间：
2019
期刊：
影响因子：
0
作者：
Centanni, Samuel W;Bedse, Gaurav;Patel, Sachin;Winder, Danny G
通讯作者：
Winder, Danny G

Noradrenergic control of the bed nucleus of the stria terminalis in stress and reward.

去甲肾上腺素能对压力和奖赏中终纹床核的控制。

DOI：
发表时间：
2013-07
期刊：
影响因子：
4.7
作者：
Flavin, Stephanie A;Winder, Danny G
通讯作者：
Winder, Danny G

mGluR8 modulates excitatory transmission in the bed nucleus of the stria terminalis in a stress-dependent manner.

mGluR8 以应激依赖性方式调节终纹床核中的兴奋性传递。

DOI：
发表时间：
2011-07
期刊：
影响因子：
0
作者：
Gosnell, Heather B;Silberman, Yuval;Grueter, Brad A;Duvoisin, Robert M;Raber, Jacob;Winder, Danny G
通讯作者：
Winder, Danny G

Corticotropin releasing factor and catecholamines enhance glutamatergic neurotransmission in the lateral subdivision of the central amygdala.

促肾上腺皮质激素释放因子和儿茶酚胺增强中央杏仁核外侧部分的谷氨酸能神经传递。