Publication:

Evaluation of antidepressant activity of ondansetron alone and in combination with fluoxetine-an experimental study

Background Direct antagonism at 5HT3 receptor site may be associated with antidepressant activity as conventional antidepressants also possess affinity for central 5HT3 binding site. So in this study, an effort is made to investigate the antidepressant effect of ondansetron (OND), a selective 5HT3 antagonist, alone and in combination with fluoxetine (FLX).

Methods Acute and chronic models of Forced swimming test (FST), tail suspension test (TST), open field test (OFT) and mice brain serotonin estimation  by UV spectrophotometry were applied for the evaluation of antidepressant activity.

Results In FST and TST (acute and chronic models), ondansetron showed statistically significant antidepressant activity (p<0.05) as compared to control. The combination groups (OND 0.25 mg/kg + FLX 5mg/kg & OND 0.5 mg/kg + FLX 5 mg/kg) showed statistically significant antidepressant activity (p<0.05) as compared to fluoxetine (5 mg/kg) and ondansetron (0.25 mg/kg and 0.5 mg/kg) in FST and TST (acute and chronic models). Open field test in chronic study showed ondansetron (0.25 mg/kg and 0.5 mg/kg) increases number of central squares crossed as compared to control which is statistically significant (p<0.05). The combination group (OND 0.25 mg/kg + FLX 5 mg/kg) showed significantly increased (p<0.05) number of central squares crossed as compared to fluoxetine (5 mg/kg). The combination group (OND 0.5 mg/kg + FLX 5 mg/kg) showed significantly increased (p<0.05) brain serotonin compared to control, ondansetron (0.25 mg/kg and 0.5 mg/kg) and fluoxetine (5 mg/kg).

Conclusions Our study concludes that ondansetron alone and in combination with fluoxetine possesses significant antidepressant activity in animal models of depression.