The role of cortisol in the pathogenesis of post-traumatic stress disorder and pharmacocorrection with melatonin

Annotation. Post-traumatic stress disorder (PTSD) is one of the key factors contributing to the development of metabolic and neurodegenerative disorders due to hypercortisolemia, which induces neuroinflammation and reduces neuroplasticity. The aim of this study was to evaluate the effectiveness of oral melatonin administration as an adjuvant in the treatment of PTSD by assessing its impact on cortisol, pyruvate, interleukin-6 (IL-6) levels, and behavioral changes in rats following chronic immobilization stress. The study involved 15 mature male non-linear white rats, divided into three groups (n=5): Group 1 – control, Group 2 – stress, Group 3 – stress with melatonin correction. Stress was simulated for 21 days using a 12-hour immobilization technique followed by a 12-hour recovery period; Group 3 received melatonin intragastrically at a dose of 5 mg/kg. Cortisol, pyruvate, and IL-6 concentrations were measured in blood serum, and behavioral responses were assessed using the Open Field test. Data were analyzed using Student's t-test in Statistica 6.0. Cortisol levels in stressed rats increased to 13.80±0.33 nmol/L compared to 1.66±0.20 nmol/L in the control group; melatonin reduced this indicator by 20%. Pyruvate concentration increased by 89.8% in Group 2 and decreased by 29% after melatonin administration. IL-6 levels increased under stress but were reduced by 43.6% with melatonin treatment. Behavioral tests showed reduced ambulation (center — by 70.83%, periphery — by 68%), exploratory activity (climbing — by 70%, rearing — by 86.21%), and increased grooming by 50% in the stress group. These changes were less pronounced in the melatonin group. Melatonin demonstrated neuroprotective, anti-inflammatory, and anxiolytic effects. The results support the feasibility of using melatonin as an adjuvant in the pharmacological correction of stress-induced disorders. Further studies should focus on determining optimal dosing, clarifying mechanisms of action, and evaluating therapeutic efficacy in clinical settings. The results of the study may contribute to the development of new approaches for correcting stress-induced metabolic and neurodegenerative disorders, particularly in the context of PTSD. The data obtained may also be valuable for designing novel strategies involving the use of melatonin as an adjuvant in the treatment of stress-related disorders.