Corticosterone differentially modulates time-dependent fear generalization following mild or moderate fear conditioning training in rats

Stressful and emotionally arousing experiences create strong memories that seem to lose specificity over time. It is uncertain, however, how the stress system contributes to the phenomenon of time-dependent fear generalization. Here, we investigated whether the glucocorticoid hormonal system affects the specificity of contextual fear memories at several timepoints. We trained male Wistar rats on the contextual fear conditioning (CFC) task using two footshock intensities (mild CFC, 3 footshocks of 0.3 mA, or moderate CFC, 3x 0.6 mA) and immediately after the training session we administered corticosterone (CORT-HBC) systemically. We first tested the animals in a novel context and then in the training context at different intervals following training (2, 14, 28 or 42 days). By measuring freezing in the novel context and then contrasting freezing times shown in both contexts, we inferred contextual fear generalization for each rat, classifying them into Generalizers or Discriminators. Following mild CFC training, the glucocorticoid induced an increased discriminative contextual memory that lasted from two up to 28 days. In contrast, after moderate CFC training, CORT-HBC facilitated contextual generalization at 14 days, compared to the control group that maintained contextual discrimination at this timepoint. For this training intensity, however, CORT-HBC did not have any effect on recent memory specificity. These findings indicate that manipulating glucocorticoid levels after mild or moderately arousing experiences may differentially modulate memory consolidation and time-dependent fear generalization.