The chronic use of alcohol provokes long-term changes in gene and protein expression that allow neurons to adapt through homeostatic alterations in distinct signaling pathways. Among the principal transduction pathways altered by alcohol consumption are those involving receptor tyrosine kinases (which are commonly activated by interaction with growth factors such as EGF, GDNF, BDNF, and insulin among others), serine–threonine kinases (which are mostly intracellular such as PKA, PKC, ERKs, AKT, GSK3, and mTOR, but can also be receptors, e.g., TGFβR), and protein–protein interactions among scaffolding proteins and associated binding partners (examples of scaffolding proteins affected by ethanol are RACK1, PSD95, and Homer2; Ron and Messing, 2011). These signaling pathways are often implicated in the regulation of a variety of transcription factors that consequently affect the expression and activity of many genes (Miranda et al., 2010). Expression profiling studies in postmortem brains of human alcoholics have shown that the transcriptional reprogramming that takes place is brain area-specific and may reflect both preexisting differences in gene expression and alterations in response to alcohol consumption (Mayfield et al., 2008; Gorini et al., 2011).
