mice. Remarkably, the authors showed that neuroinflammatory responsive genes can be seen across all brain regions at 0–8 h after the beginning of alcohol withdrawal, while sustained over-representation for subset groups of genes related to neurodevelopment and synaptic plasticity (such as Bdnf) and to histone acetylation (such as HDAC4 and HDAC6) and histone/DNA methylation are found at 3- to 7-day-withdrawal periods specifically in the PFC and the HPC. These results illustrate how transient and persistent histone acetylation changes could serve as a key mechanism for tight regulation of the expression of large sets of genes within specific brain regions of animals predisposed to excessive ethanol drinking or exposed to protracted abstinence. A functional disconnection of the CeA–PFC circuit during abstinence (72 h) and renewed access to alcohol has been recently implicated in long-lasting PFC-dependent cognitive dysfunction and the development of anxiety-like behavior, and more specifically, the resulting PFC hypofunction was shown to facilitate the transition from moderate to excessive and uncontrolled alcohol intake in rats (46).
