The current data suggest a role for the GABAA α2-subunit in mediating the sedative and ataxic effects of acute ethanol administration. Deletion of this subunit resulted in a decreased ability to maintain walking on a Rotarod apparatus under ethanol treatment, decreased motor strength as measured in the wire hang test, and a greater duration of the loss of righting reflex. In response to an acute ethanol challenge, KO animals showed lower locomotor activity compared to WT at the highest dose, further suggesting increased sedation in the KO. It should be noted that locomotor activity was measured for five minutes immediately following ethanol injection, to capture the period during which ethanol is activating. Thus, the doses administered to induce locomotor activity may seem high in comparison to other publications that emphasise the sedative effects of the drug. Since metabolism was unaffected, the effects observed indicate an increased sensitivity to the sedative and ataxic effects of ethanol. In spite of the observed acute difference, no change in the motivation to consume an ethanol solution was observed, suggesting this increased sensitivity does not extend to the rewarding properties of ethanol.
