If the GABAAR α4 subunit were critical for ethanol seeking, then one might expect responding to decrease immediately at session onset. However, this was not what we observed. Examination of the minute-by-minute pattern of instrumental responding for ethanol during the session revealed that decreased responding occurred after subjects were reinforced multiple times. Hence, responding in the first 5 minutes of the session was equal across groups. Because we observed a decrease in responding for ethanol after subjects have the opportunity to consume the reinforcer, these findings are consistent with an effect on the consummatory, not appetitive, phase of the behavior. Hence, we conclude that the GABAAR α4 subunit is important for the reinforcing effects of ethanol. We note that we use the term ‘reinforcing effects’ in the traditional behavioral sense, i.e. the effects that maintain, or reinforce, the operant response. Reinforcing effects of orally consumed ethanol are comprised of both pharmacological effects and more temporally proximal sensory attributes experienced as the subject consumes the ethanol. Hence, the behavioral mechanism(s) underlying the effect of α4 down-regulation on ethanol intake are complicated.
