Analysis of Alcohol-Related Ingestive Behaviors in Mice

描述（由申请人提供）：乙醇（酒精）的过量消费对人类健康造成严重问题，并在世界范围内对经济产生重大负面影响，特别是在美国和俄罗斯。过度饮酒的倾向与遗传因素有关，对相关基因的发现可能有助于更好地控制饮酒。动物模型可以为发现这类基因提供有效的工具。本项目的长期目标是定位克隆影响C57BL/6ByJ （B6）和129P3/J（129）小鼠自愿乙醇消耗的基因。这包括开发同源小鼠品系来分离影响乙醇消耗的基因位点，并表征它们对乙醇的行为反应。FIRCA提案的目标是优化实验程序，并对两个亲本菌株B6和129对乙醇的化学感觉感知进行全面分析。为了实现这一点，我们将描述对乙醇的化学感觉反应的几个方面：享乐性、敏感性和味觉质量感知。我们还将研究味觉、嗅觉和三叉神经的感觉输入对乙醇引起的化学感觉反应的贡献。然后，信息量最大的测试将用于研究在母体项目中创造的基因和经济小鼠。这些实验将验证一个假设，即B6和129小鼠在自愿酒精消耗方面的差异部分取决于对乙醇的不同化学感觉感知。提出的研究也将阐明负责这种差异感知的化学感觉模式。这将有助于我们阐明遗传位点作用的机制，这将有助于鉴定相应的候选基因。在小鼠基因鉴定之后，将在未来的研究中检查其人类同源物的作用。该项目将为莫奈尔中心和巴甫洛夫研究所的科学家之间的长期合作奠定基础，并将有助于建立巴甫洛夫研究所的研究能力。这项研究将主要在俄罗斯与Zolotarev博士合作，在俄罗斯科学院的巴甫洛夫生理学研究所进行，作为巴赫马诺夫博士的NIH拨款# R01 AA011028的延伸。与公众健康的相关性：该项目的目标是发现影响酒精消费的基因，这将有助于更好地理解和控制酒精滥用。

DESCRIPTION (provided by applicant): Excess consumption of ethanol (alcohol) imposes serious problems for human health and has major negative economic impact worldwide, and in the US and Russia especially. A predisposition towards alcohol overconsumption has a genetic component, and the discovery of the genes involved may lead to better control of alcohol consumption. Animal models can provide an efficient tool for discovering such genes. The long-term goal of the parent project is to positionally clone genes affecting voluntary ethanol consumption in C57BL/6ByJ (B6) and 129P3/J (129) mice. This involves developing congenic mouse strains to isolate genetic loci affecting ethanol consumption, and characterizing their behavioral responses to ethanol. The goals of the FIRCA proposal are to optimize experimental procedures and to conduct a comprehensive analysis of chemosensory perception of ethanol in the two parental strains, B6 and 129. To achieve this, we will characterize several aspects of chemosensory responsiveness to ethanol: hedonics, sensitivity, and taste quality perception. We will also examine the contribution of the gustatory, olfactory and trigeminal sensory inputs to the chemosensory responses elicited by ethanol. The most informative tests will then be used to study congenic and consomic mice created in the parent project. These experiments will test the hypothesis that differences between B6 and 129 mice in voluntary ethanol consumption depend in part on differential chemosensory perception of ethanol. The proposed studies will also elucidate the chemosensory modalities responsible for this differential perception. This will help us to elucidate mechanisms underlying the effects of the genetic loci, which will be useful for identification of corresponding candidate genes. Gene identification in mice will be followed by examination of the role of their human orthologs in future studies. This project will set the stage for a long-term collaboration between scientists at the Monell Center and the Pavlov Institute, and will help to build research capabilities at the Pavlov Institute. This research will be done primarily in Russia at the Pavlov Institute of Physiology of the Russian Academy of Sciences in collaboration with Dr. Zolotarev as an extension of the NIH grant # R01 AA011028 of Dr. Bachmanov. Relevance to public health: The goal of this project is to discover genes affecting alcohol consumption, which will lead to better understanding and control of alcohol abuse.