Alcohol dependence can cause depression by affecting hippocampal functions. Animal models of depression display dendrific atrophy and decreased spine density in hippocampal CA3 pyramidal neurons. Astrocytes have been shown to play key roles in regulafing structural and functional plasticity in neurons. Epigenetic regulation of gene expression can be modulated by histone acetylation and DNA methylation through the acfivity histone deacetylases (HDACs) and DNA methyltrasferases (DNMTs) respectively. We hypothesize that chronic ethanol and /or withdrawal induce epigenetic changes in astrocytes, affect the release of ECM proteins, inhibit neuronal plasficity in the hippocampus, and cause depressive-like behavior, effects that may be rescued by HDAC inhibifion.