Given that chronic ethanol induces excitotoxicity and oxidative stress, it is noteworthy that ethanol-induced increases in Slc7a11 (the protein product being xCT, the cystine–glutamate antiporter) are not dependent upon exci-totoxicity or oxidative stress.167 These authors reported that ethanol itself can inhibit octamer-binding transcription factor 1’s (OCT-1) repression of the Slc7a11 promoter in vitro, which in turn elevates Slc7a11 transcription. This increase in xCT would putatively increase the import of cystine into glial cells, where it would be converted to cysteine and subsequently into gluta-thione resulting in increased glutathione and decreased neurotoxicity.58 Regarding intracellular glutamate transport, an early study168 examined the effects of continuous ethanol exposure versus exposure interspersed with repeated deprivations on these vesicular glutamate transporters. These authors reported that repeated deprivations increased vGLUT2-immunos-tained terminals in the AcbSh compared to the water control group. However, ethanol exposure did not alter the level of vGLUT1-immunos-tained terminals in this brain region. These results suggest that the presence of multiple withdrawal episodes preferentially increases vGLUT2 expression in glutamate terminals in the AcbSh of P rats.168
