NEURONAL SUBSTRATES OF ETHANOL MEDIATED BEHAVIOR

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Long-sleep (LS) and short-sleep (SS) mice have been shown to exhibit significantly different behavioral responses following ethanol exposure. The most evident of these differential responses is the length of time that an animal is unable to right itself ("sleep time") following a dose of ethanol. Long-sleep mice typically require 6 to 20 times longer than short-sleep mice to regain their righting reflex after the same dose of ethanol. While this response has been found to be mediated by the CNS, the neuroanatomical structures that mediate this difference are unknown. The goal of this project is to test candidate neuronal populations and to find other candidate neuronal populations that may mediate the diffences in loss of righting response in LS and SS mice. Experimental murine chimeras will be made between embryos from long-sleep mice and short-sleep mice. The uniqueness of this system is that each neuronal population is composed of different percentages of cells of each genotype. This allows for the response time to ethanol to be correlated with the percentage of cells of the long-sleep genotype in each neuronal populations. Several candidate populations will be examined including cerebellar Purkinje cells, hippocampal pyramidal cells and hypothalamic neurons. New candidate regions will be determined through the examination of chimeric mice in which phenotype and genotype are unmatched in the other candidate regions. The region(s) that exhibit(s) the strongest correlation between neuronal genotype and "sleep time" is a good candidate for the neuroanatomical substrate(s) of this behavioral effect following ethanol exposure. This data will provide insights into the region of the brain that underlies genetic susceptibility to ethanol. This data may be important in understanding the causes of alcoholism, as studies have suggested that the tendency for alcoholism may be mediated by neural differences in sensitivity to alcohol (Schuckit, 1994).