D-cycloserine facilitates context-specific fear extinction learning

Abstract

D-cycloserine (DCS) may facilitate fear extinction learning, but the behavioral consequences and mechanisms behind this effect are not well understood at present. In this paper, we re-analyze data from previously reported null result experiments and find that rats showing above-median extinction learning during DCS treatment benefited from the drug, whereas rats showing below-median (and in this case little) extinction learning did not. Two additional experiments found that DCS facilitated extinction learning when specifically combined with a moderate, but not a small, number of extinction trials. DCS thus facilitates extinction learning only if the behavioral procedure first engages the extinction learning process. The benefits of the drug, however, were specific to the context in which extinction was learned--i.e., DCS did not prevent or influence the renewal of fear observed when the extinguished cue was tested in the original conditioning context.

Figure 1

Mean suppression (±SEM) of above-median (left) and below-median (right) groups during the drug session and the test sessions of Experiment 1. Extinguished = rats that showed above-median extinction during the drug session; Non-Extinguished = rats below the median.

Figure 2

Mean freezing of the groups during extinction (left) and testing (middle) of Experiment 2A. The renewal test, when the CS was returned to the original conditioning context, Context A, is shown at right. DCS = d-cycloserine. Note: because the crucial comparisons are within-subject, standard error bars are not shown.

Figure 3

Mean freezing of the groups during extinction (left) and testing (middle) of Experiment 2B. The renewal test is shown at right. DCS = d-cycloserine. Experiment 2B was the same as Experiment 2A except that the 2-trial extinction group originally received conditioning with a weaker shock in order to produce a similar level of freezing during testing in Contexts B and C. Note: because the crucial comparisons are within-subject, standard error bars are not shown.