Alcoholism is a chronic, often relapsing brain disorder characterized by periods of sustained, compulsive alcohol intake, relying in part on allostatic changes within the prefrontal cortex (PFC) and limbic structures [i.e., the hippocampus (HPC) and the amygdala (AMG)] [for review, see Ref. (1)]. This circuit plays key roles in behavior and cognitive function as well as in orchestrating neuroadaptive responses to stress and anxiety. The transition from recreational to alcohol dependence and compulsive alcohol drinking takes place via neuroadaptive changes in the stress-related neural circuits, caused partly by repeated cycles of alcohol intoxication and withdrawal (2, 3). A prime mechanism that contributes to the development and maintenance of alcoholism is the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis activity (4) and the release of glucocorticoids (cortisol in humans and primates, corticosterone in rodents) from the adrenal glands. Clinical and preclinical evidence 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
