Mode-dependent effects of chemical, intermittent, and hypobaric hypoxia on HIF-1α, HIF-2α, HIF-3α, PACAP, and PAI mRNA expression in the single prolonged stress model of PTSD.

Introduction: Although hypoxic interventions are increasingly explored as non-pharmacological modulators of stress-related pathology, their ability to benefit PTSD remains poorly understood. We compared behavioural and molecular outcomes of three hypoxic regimes - intermittent normobaric hypoxia (IHT), hypobaric hypoxia (Bar), and chemical hypoxia (CH) via cobalt chloride (CoCl₂) - in rats with PTSD induced by single prolonged stress (SPS). Methods: Male albino rats ( Results: Mild IHT was the only regimen to produce robust PTSD-specific anxiolysis: PTSD+IHT animals showed a four-fold reduction in EPM freezing relative to Control+IHT (5.4 ± 4.9 vs 21.6 ± 14.9 s; Discussion: As protein-level and canonical HIF target-gene readouts were not assessed, the reported transcript changes should be interpreted as a downstream feedback signature rather than a direct index of functional HIF activity. Hypoxic modality, not hypoxia per se, determines behavioural and molecular responses in PTSD; mild IHT uniquely normalised both in traumatised animals, supporting its development as a state-dependent non-pharmacological intervention for trauma-related conditions.