Background. Post-traumatic stress disorder (PTSD) is characterised by anxiety, maladaptive stress responses, and memory disturbances. Hypoxia-inducible factors (HIFs) are transcriptional regulators involved in metabolic adaptation and BDNF signalling — processes implicated in PTSD pathophysiology. Our study aimed to characterise behavioural and region-specific molecular alterations in a rat model of PTSD, focusing on the HIF-1α, HIF-2α, HIF-3α, PACAP, and PAI-1 expression in the hippocampus and medial prefrontal cortex (mPFC). Methods. PTSD was modelled in adult male outbred rats (n = 18 PTSD, n = 24 control) using the SPS protocol: 2-hour immobilisation, 15-minute forced swimming, and diethyl ether anaesthesia, followed by a 7-day incubation period. Behavioural assessment employed the Open Field Test, Elevated Plus Maze (EPM), and Dark-Light Box. Gene expression in the hippocampus and cerebral cortex was quantified by RT-qPCR using β-actin as a reference gene. Results. SPS-exposed rats exhibited a robust anxiety-like phenotype in the EPM: freezing time was nearly three times higher in PTSD animals than controls (31.6 vs 12.8 s; p < 0.001), freezing episodes were twice as frequent (7.9 vs 4.2; p < 0.01), open arm time was reduced (26.2 vs 54.2 s; p < 0.05), open-arm head dips decreased (11.5 vs 19.9; p < 0.01), and total distance travelled was lower (0.66 vs 0.90 m; p < 0.05). Dark-Light Box confirmed avoidance behaviour: light zone entries were significantly reduced in PTSD animals (1.3 vs 2.3; p < 0.01). No significant group differences were detected in the Open Field Test. At the molecular level, hippocampal HIF-1α expression was more than doubled in PTSD animals relative to controls (6.41 vs 3.12 relative units; p = 0.028), and HIF-2α was elevated approximately 2.2-fold (57.7 vs 26.4 relative units; p = 0.036). No significant changes were found for HIF-3α, PACAP, or PAI-1 in either region, nor for any target in the mPFC. Conclusions. SPS reliably induces a PTSD-like behavioural phenotype and is accompanied by selective upregulation of HIF-1α and HIF-2α in the hippocampus — a finding not previously reported in this model. The absence of corresponding cortical changes identifies the hippocampus as one of the key regions showing hypoxia-inducible pathway activation under chronic psychological stress, while other PTSD-relevant structures (e.g., amygdala, nucleus accumbens, hypothalamus) remain to be examined. These findings are based on transcript-level data; protein-level validation is ongoing. These findings support investigation of HIF-dependent signalling as a component of PTSD molecular pathophysiology.