Background/Aim. Post-traumatic stress disorder (PTSD) involves persistent neuroplasticity alterations, likely mediated by epigenetic modifications [1]. Active DNA demethylation via TET-family enzymes produces 5-hydroxymethylcytosine (5-hmC), a stable mark crucial for neuronal function [2]. Aberrant 5-hmC patterns occur in various psychiatric conditions [3], 5-hmC dynamics in PTSD pathogenesis remain unclear. This study aimed to investigate global 5-hmC levels and Tets mRNA expression in brain in the murine PTSD model and following escitalopram treatment. Methods. As the model of PTSD, single prolonged stress (SPS) paradigm was used. Male C57BL6/J mice (n = 36) were divided into 3 groups: Control (n = 18), SPS-exposed (n = 10) and SPS-exposed, treated with escitalopram (n = 8). To validate the PTSD-like phenotype and treatment efficacy, we used the Open Field (OF), Elevated Zero Maze (EZM), and Novel Object Recognition (NOR) tests. Global 5-hmC levels were quantified via dot blot assay and Tet-family mRNA expression was measured by qPCR. Data were analyzed using Welch ANOVA with Dunnett’s T3 pos-hoc test with α set at 0.05. Results. SPS-exposed mice spent more time in the open areas of the EZM and OF, displaying a reckless phenotype, and showed decreased novelty interest in the NOR test. Escitalopram treatment reversed these changes. Hippocampal 5-hmC levels remained unchanged across all groups, while escitalopram treatment significantly reduced 5-hmC level in the mPFC, comparing to both Control and SPS-exposed groups. No Tet-family RNAs — expression changes were detected in the mPFC, whereas all Tet were downregulated in hippocampus in both SPS and escitalopram-treated groups. Conclusions. We found no direct correlation between Tet mRNA expression and global 5-hmC levels in the investigated brain regions. This discrepancy suggests that 5-hmC dynamics during PTSD and antidepressant therapy depend on post-translational regulation or cofactor availability rather than transcription.