Bidirectional selection for susceptibility to ethanol withdrawal seizures inMus musculus

Using within-family selection from a genetically heterogeneous population of HS/Ibg mice, lines and replicates have been selected for high (withdrawal seizure prone; WSP) and low (withdrawal seizure resistant; WSR) susceptibility to convulsions after withdrawal from chronic exposure to ethanol. Two nonselected control lines (withdrawal-seizure control; WSC) have also been maintained. The response was bidirectional in both replicates across 11 selected generations, WSP and WSR lines differing approximately 10-fold in seizure severity after an identical regimen of chronic exposure to ethanol. Realized heritability was found to be approximately 0.28. The phenotype appears to be polygenic in nature. The relatively low amount of inbreeding in these lines and the large response to selection should make them useful for examining the physiological basis of physical dependence on ethanol.