Stress and the HPA axis: Role of glucocorticoids in alcohol dependence

Stress has long been suggested to be an important correlate of uncontrolled drinkingand relapse. An important hormonal response system to stress-thehypothalamic-pituitary-adrenal (HPA) axis-may be involved in this process,particularly stress hormones known as glucocorticoids and primarily cortisol. Theactions of this hormone system normally are tightly regulated to ensure that the bodycan respond quickly to stressful events and return to a normal state just as rapidly. Themain determinants of HPA axis activity are genetic background, early-life environment,and current life stress. Alterations in HPA axis regulation are associated withproblematic alcohol use and dependence; however, the nature of this dysregulationappears to vary with respect to stage of alcohol dependence. Much of this researchhas focused specifically on the role of cortisol in the risk for, development of, andrelapse to chronic alcohol use. These studies found that cortisol can interact with thebrain's reward system, which may contribute to alcohol's reinforcing effects. Cortisolalso can influence a person's cognitive processes, promoting habit-based learning,which may contribute to habit formation and risk of relapse. Finally, cortisol levelsduring abstinence may be useful clinical indicators of relapse vulnerability in alcohol-dependent people.