Stress before extinction learning enhances and generalizes extinction memory in a predictive learning task.

In extinction learning, the individual learns that a previously acquired association (e.g. between a threat and its predictor) is no longer valid. This learning is the principle underlying many cognitive-behavioral psychotherapeutic treatments, e.g. 'exposure therapy'. However, extinction is often highly-context dependent, leading to renewal (relapse of extinguished conditioned response following context change). We have previously shown that post-extinction stress leads to a more context-dependent extinction memory in a predictive learning task. Yet as stress prior to learning can impair the integration of contextual cues, here we aim to create a more generalized extinction memory by inducing stress prior to extinction. Forty-nine men and women learned the associations between stimuli and outcomes in a predictive learning task (day 1), extinguished them shortly after an exposure to a stress/control condition (day 2), and were tested for renewal (day 3). No group differences were seen in acquisition and extinction learning, and a renewal effect was present in both groups. However, the groups differed in the strength and context-dependency of the extinction memory. Compared to the control group, the stress group showed an overall reduced recovery of responding to the extinguished stimuli, in particular in the acquisition context. These results, together with our previous findings, demonstrate that the effects of stress exposure on extinction memory depend on its timing. While post-extinction stress makes the memory more context-bound, pre-extinction stress strengthens its consolidation for the acquisition context as well, making it potentially more resistant to relapse. These results have implications for the use of glucocorticoids as extinction-enhancers in exposure therapy.