Integrative Neuroscience Initiative on Alcoholism

描述（由申请人提供）：这是一份针对酒精中毒综合神经科学倡议联盟（INIA）-West（通知# RFA-AA-11-006）的竞争性续期申请，旨在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。 这一多学科的倡议侧重于与基底前脑相关的大脑成瘾回路中的分子和细胞神经适应，包括腹侧纹状体中的奖励回路和扩展杏仁核中的依赖回路。INIA-West的总体假设是，奖励回路中的遗传差异和神经适应性是导致个体对过度饮酒的脆弱性差异的原因。16个研究组成部分和6个科学核心将使用动物过度饮酒模型来模拟酗酒和依赖性诱导的过度饮酒的酒精滥用障碍。INIA-West的总体目标是（1）通过使用转基因、敲除、诱导型敲除、位点特异性敲除、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测定或其他方法提名的基因靶，（二）通过使用新分子与现有FDA分子的协同作用，确定最有希望用于治疗酒精中毒的药物开发的可药物化靶点，通过招募U 01赠款和试点项目的个人，并通过使信息学集成数据集可访问，可搜索，并与其他数据库交互，为所有对酒精中毒研究感兴趣的科学家吸引新的和创新的研究人员到酒精研究领域。核心设施的建议，提供分子遗传学的支持和目标评估翻译药物的目标发展。提出了一个试点项目计划，以确定令人兴奋的新的研究领域和新的研究人员不断招聘到酒精领域。INIA计划将由行政核心与执行委员会和指导委员会密切合作，并与杰出的科学咨询委员会的持续建议。

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.