Effects of multiple exposures to D-cycloserine on extinction of conditioned fear in rats

Neurobiol Learn Mem. 2005 May;83(3):224-31. doi: 10.1016/j.nlm.2005.01.001.


Previous research has shown that an acute, post-training injection of D-cycloserine (DCS) facilitates extinction of conditioned fear in rats; however, the effects of multiple exposures to DCS in this situation are not known. In Experiment 1, rats were conditioned (light-shock pairings) and 24 h later given six extinction (light-alone) trials followed by an injection of DCS (15 mg/kg) or saline. The next day, all rats were tested for light-elicited freezing. In Experiment 2, the effect of DCS on extinction was tested in the same manner, except that rats were pre-exposed to DCS (0, 1, or 5 injections) just prior to conditioning. In Experiment 3, rats received five pre-exposures of DCS but conditioning occurred either 2 or 28 days after the last pre-exposure. The results showed that DCS facilitated extinction of conditioned freezing to the light CS when no drug pre-exposure had occurred, but pre-exposure to DCS just prior to conditioning disrupted the facilitation of extinction effect. When 28 days were interposed between pre-exposure and conditioning, the facilitatory effects of DCS on extinction were restored. These findings suggest that DCS has significant clinical value but that behavioral desensitization may occur with multiple exposures; however, desensitization is not permanent and is reduced by the passage of time.

Publication types

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

MeSH terms

  • Animals
  • Antimetabolites / administration & dosage*
  • Association Learning / drug effects
  • Conditioning, Classical / drug effects*
  • Cycloserine / administration & dosage*
  • Drug Administration Schedule
  • Extinction, Psychological / drug effects*
  • Fear / drug effects*
  • Male
  • Rats
  • Rats, Sprague-Dawley


  • Antimetabolites
  • Cycloserine