Data for "Interaction between training intensity and corticosterone treatment differentially modulate time-dependent fear generalization"

Overgeneralized fear has long been implicated in generalized anxiety (GAD) and post-traumatic stress disorder (PTSD), however, mechanisms underlying memory consolidation 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 retrieval tests. Additionally, exogenous CORT administered immediately post-training modulates memory consolidation following an inverted U-curve trendline. Here we used discriminative contextual fear conditioning (CFC) to investigate the role CORT plays in the consolidation of fear memories, focusing in memory specificity. Adult male Wistar rats were exposed to CFC training with two footshock intensities (0.3 or 0.6mA, in separate groups of animals) and were immediately treated with CORT-HBC complex (4.0mg/kg or 8.0mg/kg. Sigma-Aldrich C174) or saline (2mL/kg). Two, 14, 28 or 42 days later, rats were tested for memory specificity first in a novel context (B) and 1 min after, in the training context (A). Order (B-A) was validated by a previous pilot experiment done in our lab. Freezing time (s) was used to measure memory strength and an Index of Generalization (IG) was calculated using the formula [ (s) B / ( (s) A + (s) B)]. The range expected for IG is from 0 (optimal discrimination) to 0.6 (optimal generalization). IG Values around 0.3 are intermediate between generalization and discrimination. Following mild CFC training, the glucocorticoid induced the consolidation of an increased discriminative contextual memory that lasted from two up to 28 days. In contrast, after stronger CFC training, corticosterone elicited contextual generalization at 14 days contrarily to the control group that maintained contextual discrimination at this timepoint. On the other hand, animals treated with corticosterone after the stronger CFC training did not show any treatment effect on the recent memory retrieval test. These findings indicate that manipulating glucocorticoid levels after mild or strongly arousing experiences may differentially modulate memory consolidation and time-dependent fear generalization, possibly suggesting there may be a certain level of emotional arousal that is necessary to induce the creation of generalizable fear memories