Effects of D-cycloserine on extinction: translation from preclinical to clinical work

Biol Psychiatry. 2006 Aug 15;60(4):369-75. doi: 10.1016/j.biopsych.2006.03.084.


Administration of benzodiazepines or serotonin reuptake inhibitors in combination with behavior therapy for the treatment of many anxiety disorders has generally lead to only modest gains. In this article we suggest that pharmacotherapy aimed not at treating the symptoms of anxiety but instead aimed at improving the learning that takes place in exposure therapy might actually improve the effectiveness of exposure therapy. This idea was based on animal work showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitated extinction of fear when given either before or shortly after exposure to fearful cues, reduced return of fear that is normally seen when extinction training is followed by stress, and led to generalized extinction, where DCS given in combination with exposure to one fearful cue led to extinction to another cue previously paired with the same aversive event. These finding suggested that DCS might facilitate exposure-based psychotherapy, which was verified in a small clinical study showing that DCS facilitated exposure therapy for fear of heights in a well-controlled virtual reality environment.

Publication types

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

MeSH terms

  • Animals
  • Antimetabolites / pharmacology*
  • Antimetabolites / therapeutic use
  • Cognitive Behavioral Therapy*
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology
  • Cycloserine / pharmacology*
  • Cycloserine / therapeutic use
  • Extinction, Psychological / drug effects*
  • Extinction, Psychological / physiology
  • Fear / drug effects
  • Fear / physiology
  • Humans
  • Phobic Disorders / psychology
  • Phobic Disorders / therapy*
  • Receptors, N-Methyl-D-Aspartate / agonists*
  • Receptors, N-Methyl-D-Aspartate / physiology


  • Antimetabolites
  • Receptors, N-Methyl-D-Aspartate
  • Cycloserine