Core 2: Rodent Behavioral Core

核心 2：啮齿动物行为核心

• 批准号: 10429948
• 负责人: JENNIFER T WOLSTENHOLME
• 金额: $ 18.61万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-05 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10429948
• 关键词: Acute; Alcohol abuse; Alcohol consumption; Alcohol withdrawal syndrome; Alcoholism; Alcohols; Animal Model; Animals; Anti-Anxiety Agents; Behavior; Behavior assessment; Behavioral; Behavioral Paradigm; Bioinformatics; Biological Models; Brain; Brain region; Caenorhabditis elegans; Candidate Disease Gene; Cells; Collaborations; Complex; Constitution; Consumption; Data; Development; Diagnosis; Diet; Disease; Dose; Drosophila genus; Environment; Environmental Risk Factor; Ethanol; Exhibits; Future; Genes; Genetic; Goals; Grant; Human; Individual; Invertebrates; Investigation; Knowledge; Mediating; Modeling; Molecular; Motor; Mouse Strains; Mus; Nervous system structure; Neurobiology; Omega-3 Fatty Acids; Organism; Phenotype; Pilot Projects; Predisposition; Prevention; Rattus; Risk; Rodent; Role; Sedation procedure; Seizures; Signal Pathway; Stimulant; Stress; Testing; Transgenic Mice; Translating; Validation; Viral; Viral Vector; alcohol abuse therapy; alcohol behavior; alcohol exposure; alcohol response; alcohol risk; alcohol sensitivity; alcohol testing; alcohol use disorder; behavior test; behavioral outcome; behavioral phenotyping; behavioral response; chronic alcohol ingestion; design; dietary; dietary manipulation; endophenotype; fly; gene environment interaction; gene network; genetic manipulation; hypnotic; improved; insight; neural circuit; new therapeutic target; response; therapy development; transgene delivery

Project Summary – Core 2 Susceptibility to alcoholism has a clear genetic component. The VCU-ARC and its collaborators seeks to better understand ethanol-responsive genes by studying cross-species genetic correlates. These efforts have generated several ethanol-responsive gene candidates such as Clic4, GSK3B, and slo1. The Rodent Behavioral Core (Core 2) will expand these efforts by studying the consequences of manipulating these (and newly identified) candidate genes in a rodent behavioral battery that models specific aspects of acute ethanol sensitivity, consumption, and seeking behavior. Core 2 will use conditional genetically modified mice or viral transgene delivery to mouse or rat brain. Core 2 may also use environmental modulations to investigate gene x environment interactions on ethanol response behaviors. The intent of Core 2 is to correlate expression levels of an ethanol-responsive candidate gene to a particular behavioral outcome in order to gain a deeper understanding of the genetic basis of alcoholism. The results of Core 2 will provide valuable insight into the genetic basis of the complex behavioral and neurobiological adaptations that develop as a consequence of either acute or repeated ethanol exposure. This new knowledge will aid in the development of interventions for the prevention and/or treatment of ethanol abuse and alcoholism.

项目摘要-核心2 对酒精中毒的易感性有明显的遗传成分。VCU-ARC及其合作者寻求更好地 通过研究跨物种的遗传相关性来了解乙醇反应基因。这些努力已经 产生了几个乙醇反应基因候选，如Clic4、GSK3B和SLO1。啮齿动物 行为核心(核心2)将通过研究操纵这些(和)的后果来扩展这些努力 新发现)啮齿动物行为组合中的候选基因，模拟急性酒精的特定方面 敏感度、消费和寻求行为。核心2将使用有条件的转基因小鼠或病毒 转基因输送到小鼠或大鼠的大脑。核心2也可能利用环境调节来研究基因x 环境交互作用对乙醇响应行为的影响。核心2的意图是将表达级别关联起来 酒精反应候选基因对特定行为结果的影响，以便获得更深层次的 对酒精中毒的遗传基础的理解。核心2的结果将为我们提供有价值的见解 作为结果的复杂的行为和神经生物学适应的遗传基础 急性或反复接触酒精。这一新知识将有助于制定干预措施 预防和/或治疗酒精滥用和酒精中毒。