Influence of ethanol withdrawal on fear memory: Effect of D-cycloserine

Neuroscience. 2006 Nov 3;142(4):979-90. doi: 10.1016/j.neuroscience.2006.07.013. Epub 2006 Aug 23.


Animals made dependent via an ethanol (ETOH) -containing liquid diet (6% v/v) for 14 days were subjected to a contextual fear conditioning paradigm 3 days after the last consumption day. After conditioning, rats were subjected to four extinction trials by exposing the animals to the conditioned context and their freezing was evaluated for each trial. Immediately after the first extinction trial, animals were injected with D-cycloserine (DCS) 5 mg/kg i.p., a dose that did not influence the extinction in control rats. Spontaneous recovery of learned fear was tested seven days after the last extinction trial. The following day, animals were subjected to a reacquisition or a reinstatement procedure and their freezing responses evaluated 24 h later. The present study shows that: 1. discontinuation from chronic ETOH administration facilitated the formation of a new fear memory concomitant with a marked resistance to being extinguished, 2. administration of DCS (5 mg/kg) facilitated the extinction process only in ETOH withdrawn rats, 3. both reinstatement and reacquisition procedures restored the increased freezing in ETOH withdrawn animals after extinction, 4. DCS administered immediately after the first extinction trial prevented the increase in freezing following both reacquisition and reinstatement. The enhanced sensitivity to the facilitatory effect of DCS in ETOH withdrawn animals may be mediated by adaptive changes in N-methyl-D-aspartate (NMDA) receptor provoked by ETOH dependence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol-Induced Disorders, Nervous System / physiopathology*
  • Alcohol-Induced Disorders, Nervous System / psychology
  • Animals
  • Antimetabolites / pharmacology
  • Anxiety Disorders / chemically induced
  • Anxiety Disorders / physiopathology
  • Anxiety Disorders / psychology
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology
  • Central Nervous System Depressants / adverse effects
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Cycloserine / pharmacology*
  • Disease Models, Animal
  • Drug Synergism
  • Ethanol / adverse effects*
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Fear / drug effects*
  • Fear / physiology
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Substance Withdrawal Syndrome / physiopathology*
  • Substance Withdrawal Syndrome / psychology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology


  • Antimetabolites
  • Central Nervous System Depressants
  • Receptors, N-Methyl-D-Aspartate
  • Ethanol
  • Cycloserine