A key role for corticotropin-releasing factor in alcohol dependence

Trends Neurosci. 2007 Aug;30(8):399-406. doi: 10.1016/j.tins.2007.06.006. Epub 2007 Jul 16.


Recent data indicate that alcohol dependence induces long-term neuroadaptations that recruit a negative emotional state. This leads to excessive alcohol ingestion motivated by relief of negative emotionality. A key mechanism in this transition to negative reinforcement is a recruitment of corticotropin-releasing factor (CRF) signaling within the amygdala. Long term upregulation of CRF(1) receptors is observed in the amygdala following a history of dependence, and CRF antagonists selectively block emotionality, excessive alcohol drinking and stress-induced reinstatement of alcohol-seeking in post-dependent animals. Innate upregulation of CRF(1) receptor expression mimics the post-dependent phenotype, both with regard to emotional responses and ethanol self-administration. Therefore, the CRF system is emerging as a key element of the neuroadaptive changes driving alcoholism and as a major target for its treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological / drug effects
  • Affect / drug effects
  • Affect / physiology*
  • Alcohol-Related Disorders / metabolism*
  • Amygdala / metabolism*
  • Animals
  • Behavior, Addictive / metabolism*
  • Corticotropin-Releasing Hormone / metabolism*
  • Ethanol / pharmacology
  • Humans
  • Reward


  • Ethanol
  • Corticotropin-Releasing Hormone