Evaluation of antidepressant activity of ondansetron alone and in combination with fluoxetine-an experimental study
Keywords:Antidepressant, Ondansetron, Fluoxetine, Brain serotonin
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.
Thase ME, Howland RH. Biological process in depression: an update and integration In: Beckham EE, Leber WR, editors. Handbook of Depression. 2nd edition. New York: Guilford;1995:213-79.
The world health report. Mental health: new understanding new hope. WHO, Geneva. 2001.
Madhav SM. Epidemiological study of prevalence of mental disorders in India. Indian J Comm Med. 2001;26(4):198-200.
Yu ZF, Kong LD, Chen Y. Antidepressant activity of aqueous extracts of Curcuma longa in mice. J Ethnopharmacol. 2002;83(1-2):161-5.
Potdar V, Kibile S. Evaluation of antidepressant-like effect of citrus maxima leaves in animal models of depression. Iran J Basic Med Sci. 2011;14(5):478-83.
Srivastava SK. Letter to the editor-antidepressant activity of ondansetron, a 5HT3 antagonist. Indian J Pharmacol.1998;30:411-2.
Gupta D, Devadoss T, Bhatt SB, Gautam B, jindal A, Pandey D et al. Antidepressant-like activity of a novel serotonin type-3 (5HT3) receptor antagonist in rodent model of depression. Indian J exp Biol. 2011;49:619-26.
Greenshaw AJ. Behavioral pharmacology of 5-HT3 receptor antagonists: A critical update on therapeutic potential. Trends Pharmacol Sci.1993;14(7):265-70.
Ramamoorthy R, Radhakrishnan M, Borah M. Antidepressant-like effects of serotonin type-3 antagonist, ondansetron: an investigation in behavior -based rodent models. Behav Pharmacol. 2008;19:29-40.
Chivate AN, Chivate ND, Wadkar KA, Naikwade Ns. Comparative study of ondansetron with SSRI in some animal models of depression. J Pharm Res. 2012;5(6):2543-7.
Sanmukhani J, Anovadiya A, Tripathi CB. Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study. Drug Res. 2011;68(5):769-75.
Santosh P, Venugopal R, Nilakash A. Antidepressant activity of methanolic extract of Passiflora foetida leaves in mice. Int J Pharm Pharm sci. 2011;3(1):112-5.
Udenfriend S, Weissbach H, Clark C. The estimation of 5-Hydroxytryptamine (serotonin) in biological tissues. J.Biol Chem. 1995;215:337-44.
Shrivastava SK. Emesis and antiemetics. A Complete Textbook of Medical Pharmacology. 1st edition. Sirmour, Himachal Pradesh: Avichal;2012:1236.
Mahesh R, Kumar B, Jindal A, Bhatt S, Devadoss T, Pandey D. Antidepressant-like activity of (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone (4a), a novel 5-HT3 receptor antagonist: an investigation in behavior-based rodent models of depression. Indian J Pharmacol. 2012;44(5):560-5.
Shoeb A, Chowta M, Pallempati G, Rai A, Singh A. Evaluation of antidepressant activity of vanillin in mice. Indian J Pharmacol. 2013;45(2):141-4.
Martin P, Gozlan H, Puech AJ. 5-HT3 receptor antagonists reverse helpless behavior in rats. Eur J Pharmacol. 1992;212(1):73-8.
Blandina P, Goldfarb J, Walcott J, Green J P. Serotonergic modulation of the release of endogenous norepinephrine from rat hypothalamic slices. J Pharmacol Expl Ther. 1991;256(1):341-7.