Divergent regulation of distinct glucocorticoid systems in alcohol dependence

Alcohol. 2015 Dec;49(8):811-6. doi: 10.1016/j.alcohol.2015.04.004. Epub 2015 Apr 30.


Chronic alcohol consumption disrupts glucocorticoid signaling at multiple physiological levels to interact with several disease-related processes associated with neuroendocrine and psychiatric disorders. Excessive alcohol use produces stress-related neuroadaptations at the level of the hypothalamic-pituitary-adrenal (HPA) axis as well as within central (extra-hypothalamic) neural circuitry, including the central amygdala (CeA) and prefrontal cortex (PFC). Altered glucocorticoid receptor (GR) signaling in these areas following excessive alcohol exposure is postulated to mediate the transition from recreational drinking to dependence, as well as the manifestation of a host of cognitive and neurological deficits. Specifically, a bidirectional regulation of stress systems by glucocorticoids leads to the development of an HPA axis tolerance and a concomitant sensitization of cortical and subcortical circuitries. A greater understanding of how hypothalamic and extra-hypothalamic glucocorticoid systems interact to mediate excessive drinking and related pathologies will lead to more effective therapeutic strategies for alcohol use disorder (AUD) and closely related comorbidities.

Keywords: Alcohol-use disorder; Amygdala; Cognition; Corticotropin-releasing factor; Glucocorticoids; Prefrontal cortex.

Publication types

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

MeSH terms

  • Alcohol Drinking / metabolism
  • Alcohol Drinking / physiopathology
  • Alcoholism / metabolism*
  • Alcoholism / physiopathology
  • Amygdala / physiopathology
  • Corticotropin-Releasing Hormone / metabolism
  • Craving
  • Drug Tolerance
  • Gene Expression Regulation
  • Glucocorticoids / metabolism*
  • Humans
  • Hypothalamo-Hypophyseal System / metabolism*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Neural Pathways / physiopathology
  • Pituitary-Adrenal System / metabolism*
  • Pituitary-Adrenal System / physiopathology
  • Prefrontal Cortex / physiopathology
  • Receptors, Glucocorticoid / metabolism*
  • Recurrence
  • Signal Transduction
  • Stress, Physiological


  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Corticotropin-Releasing Hormone