Another parameter that has clearly been overlooked is the influence of gender on the genome-wide transcriptional effects of ethanol, as only two studies (by the same laboratory) have directly compared males and females so far. These two studies have examined the transcriptional effects of acute withdrawal and protracted abstinence from chronic ethanol exposure in mice selectively bred for divergent ethanol withdrawal severity (Withdrawal Seizure -Prone [WSP] and -Resistant [WSR] mice). In the first case, gene expression was analyzed in the prefrontal cortex 8 h into withdrawal from 72-h ethanol vapor inhalation [63]. Interestingly, sexual dimorphism had a stronger influence on the transcriptional response to chronic ethanol than differential susceptibility to ethanol withdrawal. Genes associated with transcription were identified in both genders, but genes involved in cell death and nucleic acid binding were preferentially regulated in females, while genes related to proteolysis and calcium ion binding were more responsive to chronic ethanol in males. Notably, induction of oxidative stress response was selectively observed in females. These findings suggest an enhanced sensitivity of females to ethanol-induced neurotoxicity, which was confirmed by histological
