Genetic sensitivity to convulsants during alcohol withdrawal has been studied in different mouse strains to determine the neurochemical mechanisms regulating the symptoms of alcohol withdrawal associated with each strain. For instance, while high-alcohol preferring B6 and low-alcohol preferring D2 mice have been shown to exhibit significant differences in voluntary alcohol intake (Metten and Crabbe, 2005), these strains also differ in their susceptibility to alcohol withdrawal. B6 mice have shown low levels of withdrawal severity, whereas D2 mice exhibit high levels of withdrawal severity (Ruf et al., 2004). Moreover, studies by Metten and Crabbe found that, compared to D2 mice, B6 mice were also less sensitive to administration of bicuculline during alcohol withdrawal (Metten and Crabbe, 2005). This reduced sensitivity in B6 mice was also observed with other pro-convulsant drugs acting on GABAA receptors, including tert-butyl-bicyclo-2,2,2-phosphorothionate (TBPS) and 5-(2-cyclohexylidene-ethyl)-5-ethyl barbituric acid (CHEB) (Metten and Crabbe, 2005). These findings led Metten and Crabbe to suggest that B6 mice have deficits in GABAergic receptor function (Metten and Crabbe, 2005).
