Ethanol, a central nervous system depressant, is one of the most widely available and commonly abused drugs. The precise signaling mechanisms by which ethanol alters cognition are still under investigation, but its binding to and modulation of GABA receptors is thought to contribute [62]. The upstream signaling pathways activated by ethanol appear to converge on chromatin in the nucleus, as circular dichronism of brain lysates from ethanol-treated rats suggest a more relaxed chromatin structure than their controls [63]. More recent studies have focused on specific brain regions involved in ethanol-regulated behavioral responses in rats. Anxiety induced by ethanol withdrawal is an important negative reinforcing factor in addicts, and is thought to be mediated in part by the amygdala. Indeed, a recent study has found that ethanol withdrawal alters HDAC activity, gene expression, and chromatin structure in this brain region, and that these changes contribute to increases in anxiety [64]. Specifically, withdrawal from chronic ethanol exposure increased HDAC activity and reduced histone acetylation in the amygdala, and when this increased HDAC activity was blocked with an HDAC inhibitor, rats failed to develop withdrawal-induced anxiety (Figure 1) [64].
