working memory noted during abstinence (31, 47). Alcohol’s effects on H4 acetylation closely paralleled effects on CREB activation in the PFC. Further, systemic delivery of corticosterone inhibitor metyrapone or local intra-PFC blockade of MRs (via spironolactone) or GRs (via mifepristone) similarly reversed long-lasting deficits in pCREB and H4 acetylation levels in the PFC and alleviated working memory deficits associated with alcohol withdrawal (31). Thus, these findings suggest that long-lasting glucocorticoid-induced neuroadaptive changes in CREB and H4 acetylation in the PFC may be involved in the enduring working memory impairments caused by prolonged alcohol consumption and withdrawal. Cumulative evidence indicates that structural and functional integrity of the HPC was also compromised in rats after prolonged alcohol exposure and even greatest alterations were found after cessation of alcohol exposure (136–138). Prolonged ethanol intake caused enduring deficits in HPC-dependent spatial reference memory in the water maze (138–140). Chronic ethanol treatment also caused long-lasting decrease of histone acetylation in the dorsal HPC. However, contrary to the PFC where there was strong relationship between alcohol-induced decrease of H4 acetylation and long-lasting working memory impairments, H4 acetylation in the HPC (the CA1 region) was decreased in behaviorally “unimpaired” alcohol-treated mice and even continued to decrease in
