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Protective Effect of Propranolol and Nadolol on PTSD‐like Behavior in Rats

Traumatic experiences are reported to cause Post Traumatic Stress Disorder (PTSD). Benzodiazepines and Selective Serotonin Re‐Uptake Inhibitors are considered as standard treatments. Although clinically useful, chronic use causes drastic side effects. Thus, there remains a necessity for improving treatment and finding preventive pharmacological interventions. While promising evidence emerged with administration of b‐adrenergic receptor antagonist Propranolol and PTSD relief, methodological limitations of the studies and efficacy issues dampened the excitement. We believe it is premature to completely eliminate the role of b‐antagonists in PTSD. Using the social defeat paradigm, we examined the effect of two b‐adrenergic receptor antagonists Propranolol and Nadolol on PTSD‐like behavior in Sprague Dawley rats. Propranolol was administered in drinking water at ~18 mg/rat/day for 36 days. Nadalol was provided in rat chow (50 g/rat/day). Social defeat (SD) was performed for 7 consecutive days. In SD, the Sprague Dawley rat was introduced into the home cage of a larger, aggressive male Long Evans (LE) rat. The LE rat perceived the Sprague Dawley rat as an intruder, leading to an attack on the rat. The Sprague Dawley rat was forced into a supine postion repeatedly, inducing depression‐like behavior. We used four rat groups; SD group, SD+ Propranolol, SD+ Nadalol, and naïve control. We performed depression‐like behavior tests 24 hours after SD or control exposures, including forced swim test (FST) and social interaction (SIT). In FST, the rat was placed into a cylindrical water‐filled container for five minutes. The total time spent immobile was recorded. Higher immobility time in the water indicates depression‐like behavior. SD rats had significantly more immobility time as compared to control rats in FST. SD rats treated with Propranolol or Nadolol did not exhibit high immobility in FST. SIT measures animal sociability. The Sprage Dawley rats were placed into an apparatus containing two chambers; an empty chamber and a chamber housing a novel rat. SD rats exhibited higher depression‐like behavior (less interaction time with the novel rat as compared to an empty cup) compared to controls. SD rats pretreated with Propranolol or Nadolol did not exhibit low social interaction when compared to SD rats alone. These results suggest that depression‐like behavior induced by SD was prevented when rats were pre‐treated with Propranolol and Nadolol.