Relationship between footshock intensity, post-training corticosterone release and contextual fear memory specificity over time

Overgeneralized fear has long been implicated in generalized anxiety and post-traumatic stress disorder, however, time-dependent mechanisms underlying memory retrieval are still not completely understood. Previous studies have revealed that stronger fear conditioning training protocols are associated with both increased post-training corticosterone (CORT) levels and fear responses at later retrieval tests. Here we used discriminative contextual fear conditioning (CFC) to investigate the relationship between post-training CORT levels and memory specificity in different retrieval timepoints. Wistar rats were exposed to CFC training with increasing footshock intensities (0.3, 0.6 or 1.0mA) and had their blood collected 30 min afterwards to measure post-training plasma CORT. After 2, 14 or 28 days, rats were tested for memory specificity either in the training or in the novel context. Regression analysis was used to verify linear and non-linear interactions between CORT levels and freezing. Higher footshock intensities increased post-training CORT levels and freezing times during tests in all timepoints. Moreover, stronger trainings elicited faster memory generalization, which was associated with higher CORT levels during memory consolidation. The 0.3mA training maintained memory specificity up to 28 days. Additionally, linear regressions suggest that the shift from specific to generalized memories is underway at 14 days after training. These results are consistent with the hypotheses that stronger training protocols elicit a faster generalization rate, and that this process is associated with increased post-training CORT release.\n\nHIGHLIGHTSStronger contextual fear conditioning (CFC) elicits higher plasma corticosterone (CORT).\n\nStrong CFC and high CORT levels increase the rate of memory generalization.\n\nWeak CFC and low CORT levels retain memory specificity up to 28 days.\n\nPost-training plasma CORT is linearly associated with remote generalized fear.