Octreotide Attenuates Anxiety-Like Behaviors and Cognitive Deficits in a Rat Model of Post-traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a long-lasting mental health condition characterized by persistent intrusive recollections, avoidance behaviors, mood and cognitive alterations, heightened arousal, and significant cognitive deficits, often accompanied by hypothalamic-pituitary-adrenal (HPA) axis dysregulation and neuroinflammation. This study evaluated the therapeutic potential of octreotide (OCT), a synthetic somatostatin analog, in a rat model of PTSD induced by foot-shock contextual fear conditioning. Male Wistar rats (n = 40) were randomly assigned to four groups (n = 10/group): Saline/No Stress (control), OCT/No Stress (drug alone), Saline/PTSD (model + saline), and OCT/PTSD (model + OCT). OCT was administered intraperitoneally at 50 µg/kg daily for 21 days post-induction. Behavioral outcomes were assessed using the Open Field Test (anxiety-like exploration and locomotor activity), Elevated Zero Maze (anxiety-like avoidance), and Morris Water Maze (spatial learning and memory). Plasma corticosterone concentrations were recorded on Days 0, 1, 7, 14, and 21. Hippocampal TNF-α, superoxide dismutase (SOD) activity, and malondialdehyde levels were quantified post-behavioral testing via ELISA. The Saline/PTSD group displayed significantly elevated plasma corticosterone (P < 0.0001 from Day 1 onward), increased hippocampal TNF-α (P < 0.0001), decreased SOD activity (P < 0.0001), elevated MDA (P < 0.0001), reduced locomotor activity and central exploration in the Open Field Test (P < 0.0001 to P < 0.01), and impaired spatial memory retention in the Morris Water Maze probe trial (P < 0.0001). The Elevated Zero Maze did not reveal any significant differences. OCT treatment in the OCT/PTSD group significantly attenuated these alterations compared to the Saline/PTSD group, normalizing corticosterone from Day 7 onward, reducing TNF-α and MDA (P < 0.0001), restoring SOD activity (P < 0.01), and improving Open Field exploration and Morris Water Maze probe performance (P < 0.01). These findings demonstrate that OCT is associated with neuroprotective, anti-inflammatory, and antioxidant effects in a PTSD model, attenuating HPA hyperactivity, neuroinflammation, oxidative stress, and behavioral/cognitive deficits (though direct SSTR-mediated mechanisms remain to be experimentally confirmed). Given its established safety profile and clinical approval for other indications, OCT represents a promising candidate for repurposing in PTSD treatment.