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Ethanol Domain

Key People

Project Summary

Goals

The goal of the ethanol domain is to identify pedigrees, and ultimately the underlying genes, that mediate particular behavioral and physiological responses to ethanol or are involved in predisposing an individual to consume ethanol.

Approach

Within the human population, both ethanol consumption and the response to ethanol have been shown to be genetically mediated. Furthermore, there is a significant body of evidence supporting the hypothesis that specific responses to ethanol are valid predictors of whether or not an individual becomes an alcoholic. In animal models, particularly rodent models, of alcohol exposure, similar genetically mediated differences in ethanol consumption and responses to a bolus of ethanol have been consistently found. Thus, tests that evaluate these two parameters form the basis of the ethanol screen.

The initial tests are screening for a variety of behavioral and physiologic responses to a single bolus of a moderate dose of ethanol. In mice, moderate doses of ethanol typically cause motor incoordination, hyperactivity and hypothermia, as well as acting as an anxiolytic agent. Each of these responses is analyzed in a specific test. The level of anxiety of the mouse is measured in the elevated plus maze test in which two of the arms of the maze have low walls (less than 0.5 inch, the open arms) while the other two arms have high walls (6 inches, the closed arms). Anxiety is assessed in the plus maze as the relative amount of time an animal spends in the open arms compared to the closed arms. . This test is designed to identify pedigrees of mice in which ethanol is either highly anxiolytic or or pedigrees that have little or no anxiolytic effect. Motor incoordination is measured by comparing performance of a mouse before and following an ethanol challenge on an accelerating rotorod. Additionally, motor incoordination is assessed using the Majchrowicz rating scale that measures the degree of intoxication ranging from unaffected to comatose. Both the accelerating rotorod and the Majchrowicz rating scale are will identify pedigrees of mice that are either severely ataxic or pedigrees that demonstrate little ethanol-induced ataxia .

Ethanol-induced hyperactivity is evaluated by a computer monitored activity chamber that measuring the total distance traveled by a mouse in a block of time. Hypothermia is evaluated by comparing mouse core body temperature 60 minutes following ethanol injection with mouse core body temperature 24 hours following ethanol administration. Finally, blood alcohol levels are determined to investigate alter ethanol metabolism. Ethanol preference and voluntary consumption will be investigated via a standard two-bottle choice test the week following the completion of the ethanol screen.. Mice will be given free access to two water bottles, one that contains water and the other that contains an ethanol solution. Both the amount of ethanol solution that is consumed and the percentage of the consumed liquid that is ethanol is monitored daily. The purpose of this test is to identify mice that consume large amounts of the ethanol solution.