In addition, withdrawn mice having abnormal corticosterone concentration in the PFC displayed impaired working memory performance, effects that were not observed in animals still submitted to chronic alcohol consumption. Moreover, early and protracted withdrawal periods had no effect on the dynamic pattern of corticosterone response in the dorsal HPC, indicating that alcohol impacts glucocorticoid regulation in a brain region-specific fashion. During the 6-week withdrawal period, the degree of working memory impairment correlated with the magnitude of prefrontal corticosterone concentration, which is in accordance with the notion that there is a functional link between excessive corticosteroid signaling and PFC dysfunction (53–55). Many neuroimaging studies have indicated consistently that structural and functional deficits in PFC regulatory regions are associated with chronic alcoholism [for review, see Ref. (56)]. Another study using SPECT imaging showed that detoxified alcoholic patients who relapsed 2 months later displayed working memory deficits associated with low blood flow in the medial frontal lobe (57). Given the importance of frontal cortical regions in the modulation of AMG reactivity and the mediation of effective emotion regulation, weakened PFC function associated with a specific functional disconnection between the PFC and the AMG has been proposed as an early index of neuroadaptation in
