D-Cycloserine Facilitates Reversal in an Animal Model of Post-traumatic Stress Disorder

Sophie A. George, Mariana Rodriguez-Santiago, John Riley, James L. Abelson, Stan B. Floresco, Israel Liberzon

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Many psychiatric disorders are associated with cognitive dysfunction that is ineffectively treated by existing pharmacotherapies and which may contribute to poor real-world functioning. D-cycloserine (DCS) is a partial N-methyl-D-aspartate (NMDA) agonist that has attracted attention because of its cognitive enhancing properties, including in people with post-traumatic stress disorder (PTSD). Here, we examined the effect of DCS on reversal learning - a type of cognitive flexibility – following exposure to single prolonged stress (SPS), a rodent model of PTSD. Male Sprague Dawley rats (n = 64) were trained to press levers in an operant chamber, matched for performance and assigned to SPS or control (unstressed) groups. Following SPS, rats received three additional lever press sessions, followed by a side bias test on day three. One day later they learned a response discrimination rule (press left or right lever, opposite to side bias) and on a subsequent day were trained (and tested) for reversal to the opposite lever. DCS (15 mg/kg) or vehicle was administered 30 minutes prior to the reversal session. No between-group differences were found in acquisition or retrieval of the initial rule, but a significant drug x stress interaction on response discrimination reversal indicated that DCS had a greater beneficial effect on SPS rats’ cognitive flexibility than it did on performance in controls. These findings add to a growing literature on the beneficial effects of DCS for treating a wide variety of deficits that develop following exposure to extreme stress and may have implications for the development of novel pharmacotherapies for PTSD.

Original languageEnglish (US)
Pages (from-to)332-338
Number of pages7
JournalBehavioural Brain Research
StatePublished - Jul 16 2018


  • NMDA
  • Post-traumatic stress disorder
  • animal model
  • cognitive flexibility
  • reversal
  • single prolonged stress

ASJC Scopus subject areas

  • Behavioral Neuroscience


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