Responsiveness to the Effect of Fluoxetine in Male and Female Rats Exposed to Single Prolonged Stress: A Behavioral, Biochemical, Molecular and Histological Study

Background: Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine are the first-line choice in patients with PTSD. Animal studies have indicated that chronic fluoxetine exposure leads to persistent behavioral changes and neuroplasticity in the hippocampal formation and cortex. Previous studies revealed that adult female rats respond differently to trauma from adult males. Here, we have raised the question of whether there is a difference in the response of both sexes to the fluoxetine treatment. Method: In a rat model of PTSD, the Single Prolonged Stress (SPS) model, rats were exposed to SPS (restrained for 2 h, forced to swim for 20 min, and exposed to ether anesthesia) and were then kept undisturbed for 14 days. After that, SPS rats were subjected to chronic treatment with fluoxetine (10mg/kg -28 days), followed by behavioral (OLMT & ORMT), and biochemical tests, in which (Serum IGF-1 levels were measured using a Rat ELISA Kit), and the mRNA expression of anti-apoptotic factor (Bcl-2) and pro-apoptotic makers (Bax, and Caspase -3) were determined by using RT-PCR method and histological assessments by Golgi-Cox staining. Conclusion: We observed that male and female rats with PTSD, show a reduction of the levels of serum IGF-1, impaired spatial memory in a recognition location memory task and enhanced apoptotic-related factors expression in the hippocampus, and decreased hippocampal dendritic branches. Fluoxetine treatment alleviated these abnormalities in male and female SPS rats, but fluoxetine had no sex-dependent effects on these factors.  Our findings support that fluoxetine treatment can prevent the harmful effects of traumatic events in an animal model of PTSD in both sexes.