ACUTE CORTICOSTERONE ALTERS FEAR MEMORY CONSOLIDATION AND EXTINCTION IN RODENTS​

Exposure therapy (ET), which is based on extinction learning, is a frontline treatment for trauma-related disorders, though individual responses vary. Therapy resistance may arise from multiple factors, such as person-specific variations in cortisol levels (corticosterone in rodents). Cortisol levels cannot be measured in humans immediately before a traumatic experience, which is why fear conditioning animal models are commonly used. In our experiments, we investigated how acute elevation of corticosterone alters fear memory consolidation and extinction. Mice received a single subcutaneous injection of corticosterone (5 or 10 mg/kg) or vehicle before fear conditioning (FC), during which foot shocks were paired with an auditory cue. Twenty-four hours later, fear responses were assessed in a novel context with the conditioned cue using Videotrack (Viewpoint, France). The following day, mice were re-exposed to the original conditioning context, during which the conditioned cue was presented without foot shocks for 35 minutes, modeling ET. Two-way ANOVA with Dunnett’s post hoc comparisons revealed that the FC-induced freezing percentage was significantly decreased by ET. A 5 mg/kg corticosterone injection before trauma blocked the FC-induced increase in the freezing percentage, whereas a 10 mg/kg corticosterone injection was ineffective and caused resistance to ET afterwards. This suggests that a small acute increase in corticosterone levels may have a protective effect against fear memory formation, while further elevation not only compromises this effect but also impairs the efficacy of ET. This may indicate that distinct glucocorticoid signaling pathways exhibit varying sensitivities to different corticosterone levels, resulting in diverse behavioral outcomes.