Repeated binge ethanol drinking enhances electrical activity of central amygdala corticotropin releasing factor neurons in vivo

Neuropharmacology. 2021 May 15:189:108527. doi: 10.1016/j.neuropharm.2021.108527. Epub 2021 Mar 17.


Binge ethanol drinking is an increasingly problematic component of alcohol use disorder costing the United States approximately over $150 billion every year and causes progressive neuroplasticity alterations in numerous brain regions. However, the precise nature or machinery that underlies binge drinking has not yet been elucidated. Corticotropin releasing factor (CRF) neurons in the central amygdala (CeA) are thought to modulate binge drinking, but the specific circuit mechanisms remain poorly understood. Here, we combined optogenetics with in vivo electrophysiology to identify and record from CeA CRF neurons in mice during a repeated binge ethanol drinking task. First, we found that CeA CRF neurons were more active than CeA non-CRF cells during our binge drinking paradigm. We also observed that CeA CRF neurons displayed a heterogeneous spectrum of responses to a lick of ethanol including, pre-lick activated, lick-excited, lick-inhibited, and no response. Interestingly, pre-lick activated CeA CRF neurons exhibited higher frequency and burst firing during binge drinking sessions. Moreover, their overall tonic and phasic electrical activity enhances over repeated binge drinking sessions. Remarkably, CeA CRF units and pre-lick activated CeA CRF neurons did not show higher firing rate or bursting activity during water and sucrose consumption, suggesting that ethanol may "hijack" or plastically alter their intrinsic excitability. This article is part of the special issue on 'Neurocircuitry Modulating Drug and Alcohol Abuse'.

Keywords: Binge ethanol drinking; CRF; CeA; Electrophysiology; Ethanol.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / physiopathology
  • Animals
  • Binge Drinking / metabolism*
  • Binge Drinking / physiopathology
  • Central Amygdaloid Nucleus / drug effects
  • Central Amygdaloid Nucleus / metabolism*
  • Central Amygdaloid Nucleus / physiopathology
  • Corticotropin-Releasing Hormone / metabolism*
  • Ethanol / administration & dosage
  • Ethanol / toxicity*
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • Microelectrodes
  • Neurons / drug effects
  • Neurons / metabolism*


  • Ethanol
  • Corticotropin-Releasing Hormone