Effects of d-cycloserine on individual differences in relapse of fear

The major weakness of psychological and pharmacological interventions for anxiety disorders is that the fear often returns. We examined whether DCS, which has attracted considerable attention as a potential pharmacological adjunct to therapy, reduces relapse, and whether individual differences in the rate of extinction modulates its effectiveness in reducing relapse. Experimentally-naïve adult male rats received pairings of a white noise CS with a shock US, extinction to a criterion immediately followed by an injection of DCS or Saline, and then were tested for relapse of fear (renewal, spontaneous recovery, or reinstatement; in four separate experiments). The number of blocks to reach criteria in extinction was used to classify animals as “Fast” or “Slow” Extinguishers. We consistently found that while DCS reduced relapse in Fast Extinguishers, it had minimal effects on relapse in Slow Extinguishers. Importantly, the differences in the effect of DCS on Fast and Slow Extinguishers was not due to Fast Extinguishers being less susceptible to relapse as animals in both groups exhibited similar amounts of relapse when injected with saline. Relapse, of all three types tested, was consistently reduced by DCS, but only in the Fast Extinguishers. Such findings contribute to a growing literature identifying factors that could influence the efficacy of pharmacological adjuncts to exposure therapy. These results have important implications for the development of personalized treatment approaches, which recognize, and are tailored to, individual differences.