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. Because ethanol ingestion in low ranges (i.e. 0.2–0.3 g/kg) in rats has been shown to significantly alter behavior (Wolffgramm & Heyne 1995), we propose that α4 knockdown reduces self-administration because GABAAR α4 subunit-containing receptors mediate the pharmacological effects of ethanol that arise as the ethanol slowly accumulates across minutes of session time. Consistent with this hypothesis, reductions in the expression of the GABAAR α4 subunit in the NAc shell had no effect on unreinforced responding for ethanol. However, we did not demonstrate that measurable blood levels of ethanol were attained after only a few minutes of responding, which would be required to support this interpretation; it remains to be determined if this is the case. There are other behavioral mechanisms whereby α4 subunit down-regulation in the shell may reduce the reinforcing effects of ethanol. For example, α4 subunit down-regulation may affect taste reactivity, such that acceptance of ethanol is decreased. It is also possible that our findings reflect alterations is
