Control of chronic excessive alcohol drinking by genetic manipulation of the Edinger-Westphal nucleus urocortin-1 neuropeptide system

Transl Psychiatry. 2017 Jan 31;7(1):e1021. doi: 10.1038/tp.2016.293.


Midbrain neurons of the centrally projecting Edinger-Westphal nucleus (EWcp) are activated by alcohol, and enriched with stress-responsive neuropeptide modulators (including the paralog of corticotropin-releasing factor, urocortin-1). Evidence suggests that EWcp neurons promote behavioral processes for alcohol-seeking and consumption, but a definitive role for these cells remains elusive. Here we combined targeted viral manipulations and gene array profiling of EWcp neurons with mass behavioral phenotyping in C57BL/6 J mice to directly define the links between EWcp-specific urocortin-1 expression and voluntary binge alcohol intake, demonstrating a specific importance for EWcp urocortin-1 activity in escalation of alcohol intake.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal*
  • Binge Drinking / genetics*
  • Central Nervous System Depressants / administration & dosage*
  • Drug-Seeking Behavior*
  • Edinger-Westphal Nucleus / cytology
  • Edinger-Westphal Nucleus / metabolism*
  • Ethanol / administration & dosage*
  • Female
  • Gene Knockdown Techniques
  • Male
  • Mice, Knockout
  • Neurons / metabolism*
  • Self Administration
  • Urocortins / genetics*


  • Central Nervous System Depressants
  • Ucn1 protein, mouse
  • Urocortins
  • Ethanol