Analysis of Alcohol-Related Ingestive Behaviors in Mice

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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.