There is also evidence that chronic alcohol exposure alters corticosteroid levels and glucocorticoid receptors in brain. Recent studies have shown that glucocorticoid receptor expression (mRNA levels) and phosphorylation were elevated in the central (but not basolateral) amygdala in dependent compared to nondependent rats (Vendruscolo et al., 2012; Vendruscolo et al., 2015). Further, systemic and direct (central amygdala) injection of mifepristone was shown to reduce alcohol self-administration in dependent but not nondependent rats (Vendruscolo et al., 2015). Mifepristone treatment was also reported to reduce alcohol craving and consumption in a double-blind clinical laboratory-based study of alcohol dependent human subjects (Vendruscolo et al., 2015). Finally, studies in mice and rats have shown that withdrawal following prolonged alcohol consumption produced elevated corticosterone levels in certain brain regions (i.e., the prefrontal cortex and hippocampus) that persisted long after plasma corticosterone levels returned to baseline levels (Little et al., 2008). Elevations in brain glucocorticoid concentrations following chronic alcohol exposure and withdrawal not only may have significant implications for motivation to drink, but also may contribute to the cognitive deficits and neurotoxic damage that is commonly associated with alcohol dependence (Rose et al., 2010).
