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

Neuroscience. 2014 Sep 26;277:139-51. doi: 10.1016/j.neuroscience.2014.06.053. Epub 2014 Jul 3.


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.

Keywords: alcohol use disorders; animal models; dependence; glucocorticoids; hypothalamic pituitary adrenal axis; prefrontal cortex.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alcohol Drinking / physiopathology
  • Alcohol-Related Disorders / physiopathology*
  • Animals
  • Behavior, Addictive / physiopathology
  • Central Nervous System Depressants / pharmacology*
  • Ethanol / pharmacology*
  • Glucocorticoids / metabolism*
  • Humans
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiopathology*


  • Central Nervous System Depressants
  • Glucocorticoids
  • Ethanol