The CREB family of transcription factors is activated by phosphorylation; they promote neuronal survival, protecting neurons from excitotoxicity and apoptosis by regulating the transcription of pro-survival factors (Lonze and Ginty 2002; Mantamadiotis et al. 2002). Conversely, NF-κB is known widely for its ubiquitous roles in inflammatory and immune responses (O’Neill and Kaltschmidt 1997). Accordingly, NF-κB and CREB have different target genes. For example, CREB targets the neuropeptide Y and brain-derived neurotrophic factor (BDNF) genes, both of which are involved in promoting neuronal growth and resilience to insults, including protection against excitotoxicity and neuronal death (Lonze and Ginty 2002). Regular excitation of neurons increases synaptic plasticity related to CREB and induces synaptic proteins and BDNF. In contrast, excessive excitation triggers activation of certain extrasynaptic receptors for the neurotransmitter glutamate (i.e., N-methyl-d-aspartate [NMDA] receptors) and excitotoxicity, resulting in either rapid or delayed neuronal death, which is associated with reduced CREB (Hardingham and Bading 2010). Chronic ethanol exposure interferes with the normal functions of CREB. Thus, the levels of CREB phosphorylation and CREB–DNA binding as well as of the target gene BDNF all
