Surprisingly, little is known about the long-lasting neuroadaptive changes of glucocorticoids caused by prolonged alcohol consumption and withdrawal within neural circuits involved in learning and memory and emotional events and about their behavioral consequences. Studies, including our own, have shown that the initial phase of alcohol withdrawal period produces elevation in both circulating and brain glucocorticoids levels (29–31). Importantly, Little and colleagues (30) were first to show that during the initial phase of withdrawal from chronic (8 months in rats) alcohol consumption, rats and mice display an abnormal, exaggerated corticosterone level selectively in the medial PFC and the dorsal HPC. Strikingly, the authors found that withdrawal-associated excessive corticosterone response in the PFC persists for up to 2 months; therefore, long after, plasma corticosterone levels returned to baseline levels. In the PFC, the sustained elevation of corticosterone concentration was associated with 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
