Chunk #14 — Introduction — 1. Epigenetic Regulation due to Histone Covalent Modifications — 1B. Alcohol and Histone Acetylation and Deacetylation Mechanisms in the Brain
CREB signaling pathways have been implicated in ethanol and other drugs of abuse phenotypes in both vertebrate and invertebrate models (Levine et al., 2005; Pandey, Roy, & Zhang, 2003; Pandey, 2003, 2004; Wang, Ghezzi, Yin, & Atkinson, 2009). In vertebrate models, CREB signaling in the amygdaloid circuitry plays an important role in regulating ethanol-related behaviors and in mediating the anxiolytic effects of ethanol (Pandey et al., 2003; Pandey, Zhang, Roy, & Xu, 2005; Pandey, 2003, 2004). In the central and medial nucleus of the amygdala, after acute administration of ethanol we observed increased CREB phosphorylation, CBP levels, histone H3 and H4 acetylation, and neuropeptide Y (NPY) expression in addition to producing anxiolytic effects. On the other hand, withdrawal from chronic ethanol exposure produced opposite effects, resulting in a reduction in CREB phosphorylation, CBP and NPY levels corresponding to development of anxiety-like behaviors (Pandey, Ugale, et al., 2008; Pandey, Zhang, et al., 2008) (Figure 2). The neurotrophin BDNF (brain-derived neurotrophic factor), a critical modulator of synaptic plasticity and a downstream target gene of CREB, has also been implicated in the comorbidity
