Long-term ethanol consumption results in the development of tolerance to many of the GABA-mediated effects of ethanol and this adaptation is usually associated with diminished GABA receptor function (reviewed by Kumar, Fleming, and Morrow 2004). Changes in GABA function after chronic ethanol treatment may be due to changes in gene regulation, assembly and trafficking or posttranslational modification. The oocyte expression system as used here does not allow us to examine changes in gene regulation as the regulatory sequences are lacking in the injected cRNA and some modulatory proteins aren’t present. However oocytes do contain many common signaling proteins, including various isoforms of PKC, which are hypothesized to regulate GABA function after ethanol treatment, so some aspects of chronic ethanol treatment on specific subunit combinations may be initially studied on oocytes. As seen in Figure 4, ethanol treatment for 16 hours significantly reduced GABA responses in oocytes injected with a 2:2:1 ratio and a 6:2:1 ratio of subunits, while not affecting current amplitude of oocytes injected with 0.5:2:1 ratios. This result suggests that the effect is specific to particular subunit ratios
