In conclusion, the current data demonstrate that deletion of the gabra2 gene encoding the GABAA α2-subunit results in an increased sensitivity to the acute sedative and ataxic effects of ethanol administration, without changing the motivation to consume ethanol. In conclusion, these observations imply a protective role of the α2-subunit against the acute motor effects of high dose ethanol but the exact mechanism remains unclear. Whilst genetic variations of the GABRA2 gene in humans have previously implicated this subunit in ethanol abuse, current data suggest that this is unlikely to be due to GABAergic manipulations directly changing motivational behaviour. Considering the complexity of the literature regarding the potential role of the GABAA α2-subunit in responses to ethanol, it may be important to consider the participation of intermediate messenger systems. In the case of a role for variations in α2-subunit containing receptors as risk factors for addiction, additional factors, such as stress, and how they interact with GABAergic inhibition may be important in producing addiction-related phenotypes.
