Alcohol, stress hormones, and the prefrontal cortex: a proposed pathway to the dark side of addiction

Chronic exposure to alcohol produces changes in the prefrontal cortex that are thought to contribute to the development and maintenance of alcoholism. A large body of literature suggests that stress hormones play a critical role in this process. Here we review the bi-directional relationship between alcohol and stress hormones, and discuss how alcohol acutely stimulates the release of glucocorticoids and induces enduring modifications to neuroendocrine stress circuits during the transition from non-dependent drinking to alcohol dependence. We propose a pathway by which alcohol and stress hormones elicit neuroadaptive changes in prefrontal circuitry that could contribute functionally to a dampened neuroendocrine state and the increased propensity to relapse-a spiraling trajectory that could eventually lead to dependence.