Post-traumatic stress disorder (PTSD) is a chronic neuropsychiatric illness caused by extremely painful and traumatic experiences. PTSD symptoms include mood disorders and impaired cognition. Sarsasapogenin (Sas) is a steroidal sapogenin with a neuroprotective profile. The current study aimed to evaluate the potential of Sas in PTSD-induced anxiety and depression using single prolonged stress (SPS) model and associated changes in adenosine, hypoxanthine, and inosine levels in frontal cortex, hippocampus, and Striatum. After exposure to SPS, selected groups of mice were treated daily with sarsasapogenin (Sas) at doses of 20, 40, and 60 mg/kg or normal saline or fluoxetine for 7 days and were evaluated for depression and anxiety-like behavior using the tail suspension test (TST) and marble burying test (MBT), respectively. Following behavioral tests, the post-mortem Str, frontal cortex, and hippocampus were screened for changes in adenosine, hypoxanthine, and inosine levels. Sas treatment significantly ameliorated depression and anxiety-like behaviors in the SPS group. Sas restored adenosine levels in the frontal cortex and striatum at 40 and 60 mg/kg doses. In addition, inosine levels were disrupted in the frontal cortex and hippocampus which were restored by Sas at all doses in the frontal cortex and at 60 mg/kg in the hippocampus. However, no significant changes in hypoxanthine levels were observed in the frontal cortex, hippocampus, or striatum. The attenuation of behavioral despair and anxious behavior by Sas may involve the modulation of adenosinergic pathways. Taken together, these findings imply that Sas is a potential candidate for the treatment of PTSD-induced behavioral despair.

Keywords: PTSD, Adenosine, Depression, SPS, Anxiety