in both humans (5–7) and rodents (4, 8, 9) have shown that acute and chronic alcohol consumption, as well as withdrawal, markedly affects plasma glucocorticoid levels. The release of glucocorticoids can influence brain function by readily crossing the blood–brain barrier and exert effects through a dual glucocorticoid binding receptor system, i.e., the type I high affinity mineralocorticoid receptors (MRs) or the type II low affinity glucocorticoid receptors (GRs) (10), which act as ligand-dependent transcription factors to modulate target gene transcription. The MRs display a restricted expression in the brain, with highest densities in the HPC (11–13). The GRs are widely distributed throughout the brain (10, 14, 15) with a predominant expression in the three areas involved in learning and memory and particularly sensitive to the effects of stress, namely, the PFC, the dorsal HPC, and the AMG (16–18). Indeed, human studies of Cushing’s syndrome have shown that sustained cortisol elevation over the years compromises the integrity of the HPC–PFC circuitry and thus influences the onset and/or the severity of cognitive decline in various tasks, including spatial, decision-making and working memory processes (19–23). Further, sustained, high local concentration of glucocorticoids is responsible for long-lasting cognitive impairments occurring several weeks after the
