lysine 8 (H3K9 and H4K8, respectively) leading to rapid elevation of NPY (mRNA and protein level) specifically in the central and medial, but not the basolateral amygdaloid, nuclei (125). The same group observed that a 2-week ethanol exposure followed by acute ethanol withdrawal (24 h) switches alcohol’s effect to anxiogenic-like responses, effects that involve a shift from HDAC hypoactivity to HDAC hyperactivity and subsequently decreased histone acetylation and transcriptional repression of NPY function in the two AMG nuclei (125, 127, 128). Correcting histone acetylation deficits in the AMG via administration of the pan HDACi TSA can reverse the rapid tolerance to the anxiolytic effects of ethanol (128) and prevent the development of alcohol withdrawal-related anxiety in rat (125). Alcohol-induced neuroadaptation in the AMG also implicated deficits of BDNF activity and its target [activity-regulated cytoskeleton-associated protein (Arc)], two key signaling factors involved in synaptic transmission and plasticity. While acute ethanol exposure caused an upregulation of BDNF–Arc signaling pathway and subsequently increased dendritic spine densities in the central and medial AMG nuclei, withdrawal from prolonged ethanol exposure or binge ethanol consumption potently inhibited BDNF and Arc expression and reduced dendritic arborization in these nuclei and other regions, leading to increased anxiety-like and
