enhanced GRs activation in mice undergoing a 2-week withdrawal period from chronic alcohol consumption (30). Further, administration of the GRs antagonist mifepristone or the dihydropyridine calcium channel nimodipine, given just prior to withdrawal from chronic alcohol exposure, not only reduced the rises in brain corticosterone but also prevented persistent memory deficits seen several weeks later in mice (24) or rats (32), suggesting that withdrawn-associated rise in glucocorticoid levels specifically within medial PFC may be an early index of maladaptive persistent behaviors in alcohol-dependent subjects. Indeed, chronic treatment with the GR antagonist mifepristone attenuated escalation of ethanol intake following intermittent ethanol vapor exposure (33) as well as the development of alcohol dependence and ultimately withdrawal-associated behavioral deficits (34). Endogenous glucocorticoids have been suggested to play an essential role in maintaining PFC-dependent cognitive functions, mainly via complex interaction with dopaminergic and glutamatergic receptors (35–37). Both human and animal studies have demonstrated that alcohol withdrawal impairs a variety of the cognitive functions during tests that require cortical prefrontal processing (38–40). As regards, pharmacological (hydrocortisone administration) or pathological (Cushing’s disease) increase of cortisol was found to predict frontal cortex-based cognitive impairments including alterations in executive processes and working memory dysfunction (19, 23, 41–43). Long-lasting
