Integrative Neuroscience Initiative on Alcoholism

描述（由申请人提供）：这是酒精中毒综合神经科学倡议联盟（INIA -West）（通告# RFA-AA-11-006）的竞争性更新申请，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。这个多学科的项目主要研究与基底前脑相关的脑成瘾回路的分子和细胞神经适应性，包括腹侧纹状体的奖励回路和扩展杏仁核的依赖回路。nia - west的总体假设是，奖励回路中的遗传差异和神经适应是导致个体对过量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中使用过度饮酒模型来模拟暴饮暴食和依赖引起的酒精滥用障碍的过度饮酒。nia - west的总体目标是：(1)通过转基因、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、体内成像和下一代测序等方法，确认表达试验或其他方法提名的基因靶点；(2)通过在动物模型中使用具有预测能力的新分子与FDA批准的现有分子相结合，确定最有希望用于治疗酒精中毒的药物开发的药物靶点；(3)通过为U01资助和试点项目招募个人，并通过使信息学集成数据集可访问、可搜索，吸引新的和创新的研究人员进入酒精研究领域；并与所有对酗酒研究感兴趣的科学家的其他数据库进行交互。提出了为药物靶点开发提供分子遗传学支持和靶点评价翻译的核心设施。提出了一项试点项目方案，以确定令人兴奋的新研究领域，并不断为酒精领域招募新的研究人员。该方案将由行政核心与执行委员会和指导委员会密切合作，并在杰出的科学咨询委员会的持续咨询下进行指导。

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.