Dynamic expression of PTSD-like behavioral and corticosterone phenotypes over time in a peripubertal rat model:...

Post-traumatic stress disorder (PTSD) frequently emerges following early-life trauma, yet the temporal dynamics of PTSD-like phenotypes and their pharmacological modulation during development remain poorly understood. In the present study, we investigated time-dependent behavioral and endocrine alterations in a peripubertal rat stress-restress model and assessed the effects of fluoxetine across early and delayed post-treatment stages. Male peripubertal rats were exposed to a combined stress-restress paradigm and treated with fluoxetine for 21 days. Anxiety-like behavior, social behavior, stress-coping behavior, and spontaneous locomotor activity were assessed immediately after treatment completion and again after a drug-free washout period, the duration of which (3-4 weeks) depended on the behavioral parameter evaluated. Serum corticosterone levels were measured as an index of hypothalamic-pituitary-adrenal axis activity. PTSD-like stress induced robust but domain-specific behavioral alterations that evolved over time. Anxiety-like behavior persisted across both observation phases but was expressed through different behavioral components at early versus delayed stages. Basal sociability was markedly reduced following stress exposure and was largely normalized by fluoxetine, whereas social novelty-related alterations were more selective and resistant to pharmacological modulation. Stress-exposed animals exhibited increased activity and reduced immobility in the forced swim test, reflecting altered stress-coping strategies rather than reduced depressive-like behavior. Consistently, spontaneous locomotor activity was elevated at early stages, indicating hyperarousal, which attenuated over time but was not robustly normalized by fluoxetine. Endocrine assessment revealed a biphasic corticosterone profile, with elevated levels in the early phase and reduced levels at the delayed stage; fluoxetine did not normalize corticosterone concentrations. These findings demonstrate that PTSD-like phenotypes induced during the peripubertal period are dynamic and strongly time-dependent, and that fluoxetine exerts selective, domain-specific effects rather than uniform normalization. The study highlights the importance of developmental stage and timing of assessment when evaluating behavioral outcomes and pharmacological efficacy in preclinical models of PTSD.