CHRONIC CORTICOSTERONE EXPOSURE BEFORE TRAUMA ALTERS GLUCOCORTICOID-SIGNALING GENE EXPRESSION IN LIMBIC SYSTEMS AND IMPAIRS TRAUMA-RELATED MEMORY FORMATION IN RODENTS

Glucocorticoid signalling plays a central role in traumatic memory formation and is often dysregulated in stress-related disorders such as post-traumatic stress disorder (PTSD). A key phase in this process is the early consolidation window, during which aversive experiences are stabilised into long-term memory through protein synthesis and glucocorticoid-responsive gene expression. To investigate how glucocorticoid dynamics shape this phase, we examined behavioural and molecular outcomes following acute versus chronic corticosterone exposure in mice. Animals received either repeated corticosterone (20 mg/kg) injections for five days before auditory fear conditioning (FC) or a single injection immediately before FC. Two hours after conditioning, the amygdala, hippocampus, and anterior cingulate cortex were dissected, and real-time qPCR quantified expressions of mineralocorticoid (Nr3c2; MR) and glucocorticoid (Nr3c1; GR) receptors, and FK506-binding protein 5 (FKBP5). In behavioural experiments, memory strength was assessed 24 hours later by measuring freezing/exploratory behaviour. Two-way ANOVA with Dunnett’s multiple comparisons test was used for statistical analysis. Chronic, but not acute, corticosterone exposure significantly reduced freezing percentages during recall, indicating impaired traumatic memory consolidation. This impairment coincided with marked hippocampal transcriptional alterations, most prominently a failure of FC-induced downregulation of MR expression, which normally marks the closure of an MR-dependent plasticity window. GR and FKBP5 exhibited modest, region-specific changes. These findings suggest that chronic corticosterone elevation before trauma sustains MR expression and extends plasticity, potentially triggering processes that inhibit memory consolidation under prolonged or excessive stress. This work is supported by the Shota Rustaveli National Science Foundation of Georgia (FR/22-26152).