Integrative Neuroscience Initiative on Alcoholism

关于酗酒的综合神经科学倡议

• 批准号: 9316132
• 负责人: MARISA ROBERTO
• 金额: $ 40.18万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9316132
• 关键词: Address; Alcohol abuse; Alcoholism; Alcohols; Amygdaloid structure; Animal Model; Animals; Area; Basic Science; Behavioral; Biological; Biological Assay; Boxing; Brain; Breeding; Charge; Communication; Communities; Core Facility; Core Grant; Data; Data Collection; Data Set; Databases; Dependence; Development; Disease; Electrophysiology (science); Ensure; Etiology; Evaluation; Funding; Gene Targeting; Genes; Genetic; Goals; Grant; Health Policy; Heavy Drinking; Human; In Situ Hybridization; Individual; Individual Differences; Informatics; Knock-out; Leadership; Link; Measures; Methods; Mission; Modeling; Molecular; Molecular Genetics; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neurosciences; Pathway interactions; Pharmaceutical Preparations; Physiological; Pilot Projects; Prevention; Progress Reports; Proteins; Public Health; Publications; RNA Interference; Recruitment Activity; Research; Research Personnel; Role; Schedule; Scientist; Site; Structure; Subgroup; System; Testing; Transgenic Organisms; Translating; Translations; Ventral Striatum; Work; addiction; alcohol research; alcoholism therapy; animal model development; basal forebrain; base; behavioral study; data sharing; genetic approach; heuristics; in vivo; in vivo imaging; innovation; insight; interest; meetings; multidisciplinary; neuroadaptation; next generation sequencing; novel; novel strategies; programs; research study; reward circuitry; small molecule; success; symposium; therapy development; web site

DESCRIPTION (provided by applicant): This is a competing renewal application for a Consortium for the Integrative Neuroscience Initiative on Alcoholism (INIA)-West (Notice# RFA-AA-11-006) to identify the molecular, cellular, and behavioral neuroadaptations that occur in specific brain neurocircuitries that result in excessive alcohol consumption. This multidisciplinary initiative focuses on the molecular and cellular neuroadaptations in brain addiction circuits associated with the basal forebrain, including reward circuitry in the ventral striatum and dependence circuitry in the extended amygdala. The overall hypothesis for INIA-West is that genetic differences and neuroadaptations in reward circuitry are responsible for individual differences in the vulnerability to the excessive alcohol consumption. Sixteen research components and six scientific cores will use excessive drinking models in animals to mimic the binge- and dependence-induced excessive drinking of alcohol abuse disorders. The overall goals of INIA-West are (1) to confirm gene targets nominated by expression assays or other methods by use of transgenic, knockout, inducible knockout, site-specific knockout, RNAi, in situ hybridization, in vivo electrophysiology, in vivo imaging, and next-generation sequencing, (2) to identify druggable targets that are most promising for medication development for the treatment of alcoholism by use of novel molecules in concert with molecules with existing FDA approval in animal models with the most predictive ability, and (3) to attract new and innovative investigators to the field of alcohol research by recruiting individuals for U01 grants and Pilot projects and by making the informatics integrated datasets accessible, searchable, and interactive with other databases for all scientists interested in alcoholism research. Core facilities are proposed that provide molecular genetic support and target assessment translation for medications target development. A Pilot Project program is proposed to identify exciting new areas of research and the continual recruitment of new investigators to the alcohol field. The INIA program will be directed by the Administrative Core in close cooperation with the Executive Committee and Steering Committee and with the continual advice of a distinguished Scientific Advisory Board.

描述(由申请人提供)：这是酒精中毒综合神经科学倡议(INIA)-WEST联盟(通知#RFA-AA-11-006)的竞争性续签申请，以确定导致过量饮酒的特定脑神经回路中发生的分子、细胞和行为神经适应。这一多学科的研究重点是与基底前脑相关的大脑成瘾环路中的分子和细胞神经适应，包括腹侧纹状体的奖赏环路和延伸杏仁核的依赖环路。INIA-West的总体假设是，遗传差异和奖励回路中的神经适应是导致个体对过度饮酒易感性差异的原因。16个研究组成部分和6个科学核心将在动物身上使用过量饮酒模型来模拟酗酒和依赖诱导的过度饮酒滥用障碍。INIA-WEST的总体目标是(1)通过使用转基因、基因敲除、可诱导基因敲除、位置特异性基因敲除、RNAi、原位杂交、体内电生理学、体内成像和下一代测序来确认通过表达分析或其他方法提名的基因靶点，(2)通过在具有最大预测能力的动物模型中使用新分子与现有FDA批准的分子相结合，识别最有希望用于酒精中毒药物开发的可用药靶点，以及(3)吸引新的和创新的研究人员进入酒精研究领域，为U01拨款和试点项目招募个人，并使信息学综合数据集可供所有对酒精中毒研究感兴趣的科学家访问、搜索并与其他数据库互动。提出了为药物靶标开发提供分子遗传学支持和靶标评估翻译的核心设施。提出了一个试点项目计划，以确定令人兴奋的新研究领域，并不断向酒精领域招募新的调查人员。INIA计划将由行政核心指导，与执行委员会和指导委员会密切合作，并得到杰出的科学顾问委员会的持续建议。