D-cycloserine and the facilitation of extinction of conditioned fear: consequences for reinstatement

Behav Neurosci. 2004 Jun;118(3):505-13. doi: 10.1037/0735-7044.118.3.505.


Several recent studies have reported that D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, facilitates extinction of learned fear in rats. Other studies have shown that representation of the unconditioned stimulus (US) can reinstate learned fear after extinction. This study examined whether this reinstatement effect occurs in Sprague-Dawley rats given DCS at the time of extinction. Results showed that saline-treated rats exhibited the reinstatement effect but DCS-treated rats did not (Experiments 1 and 2). This lack of reinstatement in DCS-treated rats was not due to residual effects of DCS on either US or context processing (Experiment 3). Overall, these results (a) raise questions about the mechanisms underlying DCS facilitation of extinction and (b) suggest that DCS might have substantial practical benefit.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antimetabolites / pharmacology
  • Behavior, Animal
  • Conditioning, Psychological / drug effects*
  • Cycloserine / pharmacology*
  • Dose-Response Relationship, Drug
  • Electroshock / adverse effects
  • Extinction, Psychological / drug effects*
  • Fear / drug effects*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reflex, Startle / drug effects*


  • Antimetabolites
  • Cycloserine