Figure 3. Effects of alcohol exposure on histone acetylation.

A) Acute ethanol causes an increase in ACSS2 activity which is responsible for converting acetate to acetyl-CoA, a perquisite for histone acetylation, as well as increasing expression of the histone acetyltransferases CBP and P300 and decreasing histone deacetylase activity (HDAC). This results in an open chromatin structure which increases neuropeptide y (Npy) and activity-regulated cytoskeleton-associated protein (Arc), which could explain some of the anxiolytic effects of ethanol. B) Chronic alcohol and withdrawal increases HDAC activity and decreases CBP and P300, leading to a condensed chromatin structure. This corresponds to a decrease of Npy, Arc, brain derived neurotrophic factor (BDNF) and gamma aminobutyric acid alpha1 subunit (Gabra1). Functionally, in prefrontal cortex pyramidal neurons and the VTA, there is a decrease in GABA transmission and behaviorally both anxiety-like behavior and alcohol consumption are elevated. Treatment with HDAC inhibitors, such as Trichostatin A (TSA) restores chromatin and gene expression to a normal level, decreases ethanol consumption and prevents anxiety-like behavior and decreases GABA transmission. Some of these effects are observed when alcohol is given during key stages of development such as prenatal or adolescence.