Genes involved in cellular stress responses are also sensitive to alcohol exposure. The glucocorticoid receptor (NR3C1) was down-regulated in hippocampus from alcoholics, whereas negative regulators of the pathway (FK506 binding proteins) were increased over two-fold (McClintick et al., 2013). The TXNIP gene encoding thioredoxin-binding protein, which can be transcriptionally induced by glucocorticoids, was increased in alcoholics. TXNIP acts as a major regulator of cellular redox signaling and protects cells from oxidative stress, suggesting an enhanced cellular stress response induced by chronic alcohol exposure. Moreover, alcohol abuse, chronic drinking and early stages of withdrawal increased the expression of genes involved in behavioral stress responses, such as cortisol-releasing-hormone (CRH), which can activate glucocorticoid receptors and enhance expression of downstream inflammatory genes (e.g. IL1B, TGFB1) (Armario, 2010). Cortisol is known to modify learning and memory (Stephens and Wand, 2012). Exposure to high levels of behavioral stress and increased cortisol can transiently block memory retrieval (van Stegeren, 2009), with retrieval of emotional memory more strongly affected than that of neutral memory. Potential effects on emotionally charged memory and habit learning may be particularly relevant
