权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The Role of GABA Co-release from Dopamine Neurons in Ethanol Consumption

多巴胺神经元 GABA 共释放在乙醇消耗中的作用

基本信息

批准号：
10116964
负责人：
Konstantin Kaganovsky
金额：
$ 3.84万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10116964
关键词：
Age Alcohol consumption American Atlases Automobile Driving Brain Brain region Cells Cessation of life Corpus striatum structure Dendrites Distal Dopamine Dopaminergic Cell Drug Targeting Economics Electrophysiology (science)Ethanol FDA approved Feedback Future Genes Genetic study Glutamates Health Heavy Drinking Human Human Genetics Image Individual Knock-out Lead Link Liver Modeling Mus Mutation Neurons Neurosciences Research Neurotransmitters Pharmaceutical Preparations Play Proteins Public Health Rattus Retina Rewards Risk Factors Role Signal Transduction Substance abuse problem Substantia nigra structure Synapses Techniques Testing Tissues Transgenic Mice Translational Research Viral World Health Organization acetaldehyde dehydrogenase alcohol misuse alcohol use disorder cell type disability dopaminergic neuron drinking behavior experimental study gamma-Aminobutyric Acid health management in vivo insight neurophysiology neurotransmission novel novel strategies optogenetics pars compacta premature problem drinker social treatment strategy two-photon

项目摘要

PROJECT SUMMARY Alcohol use disorder is a serious public health concern, yet its cause remains elusive; we still do not fully understand the neurophysiological mechanisms that drive EtOH consumption. All addictive drugs activate dopamine (DA) neurons, and this was assumed to only cause a synaptic increase of the neurotransmitter DA. However, recent evidence suggests that DA neurons also release the inhibitory neurotransmitter GABA, which equips DA neurons with another level of control over the striatum. Using transgenic mice, viral manipulations, and EtOH drinking behavior, the experiments proposed here will provide a mechanistic account of the role of GABA co-release from DA neurons in EtOH consumption. The results will also provide another level of mechanism – using two-photon imaging, optogenetics, and electrophysiology, the post-synaptic consequences of DA and GABA co-release on dendritic excitability will be defined. The mechanistic insight gained from these studies could inform novel treatment strategies for alcohol use disorder.

项目摘要酒精使用障碍是一个严重的公共卫生问题，但其原因仍然难以捉摸;我们仍然不完全了解。了解驱动EtOH消耗的神经生理机制。所有成瘾药物都会激活多巴胺（DA）神经元，这被认为只会导致神经递质的突触增加 DA.然而，最近的证据表明，DA神经元也释放抑制性神经递质 GABA，它使DA神经元对纹状体具有另一种控制水平。使用转基因小鼠，病毒操纵，和乙醇饮用行为，这里提出的实验将提供一个机械帐户的作用，GABA共释放DA神经元在乙醇消耗。结果还将提供另一个层次的机制-使用双光子成像，光遗传学，电生理学，DA和GABA共同释放对树突兴奋性的突触后后果将被定义。从这些研究中获得的机制见解可以为新的治疗策略提供信息酒精使用障碍