Ethanol enhances reactivated fear memories

Neuropsychopharmacology. 2008 Nov;33(12):2912-21. doi: 10.1038/npp.2008.13. Epub 2008 Feb 20.


Although ethanol has been shown to impair acquisition of memory, its effect on consolidated memories is not clear. Recent reports revealed that memory retrieval converted consolidated memory into a labile state and initiated the reconsolidation process. In the present study, we have demonstrated the effect of ethanol on reactivated fear memory. We used contextual fear conditioning where rats were conditioned with mild footshock, re-exposed to the training context for 2 min, immediately injected with ethanol or saline, and finally tested 48 h after re-exposure. Ethanol-treated groups demonstrated longer freezing and the effect lasted for 2 weeks. Reactivation is necessary for this effect. Injection of ethanol itself did not induce a fearful response. Reactivated and ethanol-treated rats exhibited longer freezing than non-reactivated controls, suggesting that ethanol does not inhibit the memory decline but facilitates the fear memory. Two minute re-exposures induced no or little extinction. The effect of ethanol was specific for 2-min reactivation, which induces reconsolidation. Moreover, we found that picrotoxin inhibited the memory enhancement that was produced by ethanol administered just after the reactivation. These studies demonstrate that ethanol enhances reactivated contextual fear memories via activation of GABA(A) receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol-Induced Disorders, Nervous System / metabolism
  • Alcohol-Induced Disorders, Nervous System / physiopathology
  • Animals
  • Brain / drug effects*
  • Brain / metabolism*
  • Brain / physiopathology
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology
  • Central Nervous System Depressants / pharmacology
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Disease Models, Animal
  • Ethanol / pharmacology*
  • Fear / drug effects*
  • Fear / physiology
  • GABA Antagonists / pharmacology
  • Learning / drug effects
  • Learning / physiology
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / metabolism


  • Central Nervous System Depressants
  • GABA Antagonists
  • Receptors, GABA-A
  • Ethanol
  • gamma-Aminobutyric Acid