Ethanol dependence in mice: Direct and correlated responses to ten generations of selective breeding

With the goal of producing an animal model of alcohol dependence, genetic selection in mice for severity of the alcohol withdrawal syndrome is underway. Ten generations of selection have been completed, and the lines selected for severe or mild expression of the withdrawal syndrome following a 9-day ethanol treatment period are significantly different from each other. The index of selection is the unrotated first-principal-component score derived from the intercorrelations among seven different measures of severity of ethanol withdrawal. Across the generations, mice from all six closed mating populations have increased their mean consumption of alcohol considerably. This seems to be the result of natural selection operating concurrently with artificial selection. When animals from generation 9 were used to test for possible correlated responses to selection, there was an indication that animals selected for mild expression of withdrawal symptoms are also less sensitive to an acute dose of ethanol.This work was supported by NIAAA Grant AA-03527.