D-cycloserine facilitates extinction of learned fear: effects on reacquisition and generalized extinction

Biol Psychiatry. 2005 Apr 15;57(8):841-7. doi: 10.1016/j.biopsych.2005.01.023.


Background: d-cycloserine (DCS) facilitates extinction of learned fear. The aim of this study was to examine whether DCS 1) affects reacquisition of fear (Experiment 1) and 2) produces generalized extinction of fear (Experiment 2).

Methods: Following fear conditioning, where a light or a tone conditioned stimulus (CS) was paired with a white-noise burst unconditioned stimulus (US), rats received nonreinforced exposure to one CS (i.e., extinction training). Fear was assessed by measuring CS-elicited freezing, a species-specific defense response.

Results: Rats given DCS exhibited facilitated extinction of fear but were able to reacquire fear of that CS in a similar manner as saline-treated control animals (Experiment 1). Furthermore, DCS-treated rats exhibited generalized extinction (i.e., they were less fearful of a non-extinguished CS) in comparison to controls (Experiment 2).

Conclusions: DCS facilitates extinction of learned fear to the extinguished CS, but also appears to reduce fear of a nonextinguished CS. These findings suggest that this drug may have substantial clinical value in the treatment of anxiety disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites / pharmacology*
  • Avoidance Learning / drug effects
  • Calorimetry, Differential Scanning
  • Conditioning, Psychological
  • Cycloserine / pharmacology*
  • Excitatory Amino Acid Agonists / pharmacology
  • Extinction, Psychological / drug effects*
  • Fear / drug effects*
  • Learning / drug effects*
  • Male
  • N-Methylaspartate / pharmacology
  • Rats
  • Rats, Sprague-Dawley


  • Antimetabolites
  • Excitatory Amino Acid Agonists
  • N-Methylaspartate
  • Cycloserine