The proposed research will examine the effects of acute and chronic ethanol administration on young, adolescent mice. The long-term objectives are to characterize initial sensitivity, tolerance acquisition and withdrawal reactions in adolescent mice. The animal model to be used in these experiments consists of two lines of mice developed by selective breeding techniques at the Institute for Behavioral Genetics in Boulder, Colorado. These lines, the so-called Long Sleep (LS) and Short Sleep (SS) mice differ in initial (central nervous system) sensitivity to ethanol. This research will assess the influence of genotype and age on ethanol sleep time, blood and brain ethanol at the time of loss of the righting response, blood and brain ethanol at the time of regaining the righting response, and ethanol metabolism. Chronic ethanol treatment with a liquid diet will be followed by assessment of tolerance and withdrawal reactions using a multiple variable test battery including measurements of handling seizures, respiration rate, rotarod performance, heart rate, body temperature and blood ethanol levels. Although alcohol use is increasing among human adolescents, very little is known concerning the effects of alcohol on the young. However, previous studies conducted by the principal investigator and others have demonstrated the importance of both genetic factors and age on the response of mice to ethanol. The proposed research is a logical extension of these earlier studies and should provide data which will be useful in determining how ethanol affects young mice of differing genetic backgrounds.
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