ROLE OF ACETALDEHYDE IN CENTRAL ACTIONS OF ETHANOL

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DESCRIPTION: The first specific is designed to discover and identify the enzymes responsible for the oxidation of ethanol to acetaldehyde in the brains of mice. The second aim is to study the mechanisms by which the accumulation of acetaldehyde in the brain alters the effect of ethanol in the central nervous system. Preliminary results provide a correlation between ethanol induced hypnosis (sleep time) and brain acetaldehyde levels. It is a collaborative project between Dr. Sergey Zimatkin and his colleagues at the Institute of Biochemistry, Grodno, Belarus in the former Soviet Union and Dr. Richard Deitrich and his colleagues at the Alcohol Research Center at the University of Colorado Health Sciences Center. The Institute of Biochemistry in Grodno has long been known for its studies on the metabolism and actions of ethanol and have the expertise to carry out the biochemical studies necessary for this project. The animal breeding and behavioral tests will be conducted at the University of Colorado Alcohol Research Center. This Center has selectively bred mice for differential responses to ethanol and has a great deal of experience in the behavioral and genetic characterization of such animals. In addition, we now have acatalasemic mice as well as Cytochrome P450 2EI knockout mice. Since both catalase and this cytochrome have been implicated in ethanol oxidation, these knockout mice will be especially useful.