The Potential Role of Glucocorticoids and the HPA Axis in Alcohol Dependence

The hypothalamic-pituitary-adrenal (HPA) axis is an important component of the stress-response system. The HPA axis carefully orchestrates a rapid hormonal stress response and subsequent return to homeostasis once the stressor has passed. However, HPA axis dysregulation that results in hypo-or hyperresponsive production of the stress hormone cortisol has been associated with hazardous alcohol use and dependence. Cortisol interacts with the brain's reward system, may contribute to habit formation and promote habit-based learning, and may trigger important epigenetic events to potentially increase risk for, development of, and maintenance of alcohol use disorders. Further, cortisol levels during initial alcohol abstinence may indicate relapse vulnerability. Therapeutic advances currently include compounds that target brain stress systems that theoretically can reduce cortisol levels or block the effects of cortisol in the body. The implications of HPA axis dysregulation associated with alcohol use disorders are discussed.