Genetically modified mouse models have contributed to our understanding of the relationship between GABAA receptor subtype expression and CNS hyperexcitability. Recent work in the ethanol-insensitive (S270H, L277A) α1-GABAA receptor knockin animals indicates that α1 subunits play a significant role in CNS excitability. Male knockin mice display enhanced ethanol withdrawal-related handling-induced convulsions (HICs) (Werner et al. 2009). Additionally, a number of mortalities were observed in the knockin mice that were attributable to seizure severity, whereas mortalities were not observed following ethanol exposure in control mice. However, knockin mice exhibited spontaneous seizures that may have kindled ethanol-withdrawal seizure susceptibility. Interestingly, α1-GABAA receptor knockout mice had increased seizure susceptibility to bicuculline as well as more severe seizures and death (Kralic et al. 2002a). In other studies, α1-GABAA receptor knockout mice did not differ in withdrawal-related HICs, but these mice consumed less ethanol prior to withdrawal than wildtype control mice, possibly masking a difference between mouse lines (Blednov et al. 2003b). Studies have also assessed the role of β subunits in ethanol withdrawal seizure severity. β2-GABAA receptor knockout mice had increased HICs after chronic
