Published: 2021-05-25

Antidepressant like activity of Buspirone but not of ondansetron when administered in combination with Fluoxetine or Desipramine in mice

Veena Verma, Biswadeep Banerjee, Ashish K. Mehta


Background: The involvement of one or more 5-HT receptor sub-types in the pathophysiology of depression is still unclear. The study was performed to investigate the effect of ondansetron and buspirone on depression, and their interaction with fluoxetine or desipramine.

Methods: The mice were administered ondansetron, buspirone alone and in combinations with fluoxetine or desipramine for 21 days, and the antidepressant effect was assessed by the immobility period and the sucrose consumption, on the tail suspension test (TST) and the chronic mild stress (CMS) models, respectively.

Results: Both ondansetron and buspirone when given alone demonstrated slight non-significant decrease in the immobility time in TST model. Ondansetron when given in combination with fluoxetine (10 mg/kg; i.p.) and desipramine (15 mg/kg; i.p.), showed significant decrease in immobility time in comparison to the control group only. On the other hand, both the combinations of buspirone, either with fluoxetine or desipramine showed significant decrease in the immobility time when compared to the respective group. In CMS, the fluoxetine, desipramine, ondansetron, and buspirone showed gradual increase in the sucrose consumption, at the end of 4th, 5th, and 6th week, but the significant effect was observed only at the end of 6th week, as compared to the control. The combination of buspirone with desipramine but not with fluoxetine showed significant increase in sucrose consumption when compared to respective group.

Conclusions: Therefore, the study indicates that both buspirone and ondansetron have a potential antidepressant like action, although buspirone has shown better antidepressant activity than ondansetron as observed in various combination groups.


Ondansetron, Buspirone, Desipramine, Fluoxetine, Tail suspension test, Chronic mild stress

Full Text:



Sadock BJ, Sadock VA. Kaplan and Sadock's Synopsis of Psychiatry, 10th edition. 2007: 527-528.

Hindmarch I. Expanding the horizons of depression beyond the monoamine hypothesis. Hum Psychopharmacol. 2001;16:203­18.

Ceglia I, Acconcia S, Fracasso C, Colovic M, Caccia S, Invernizzi RW. Effects of chronic treatment with escitalopram or citalopram on extracellular 5-HT in the prefrontal cortex of rats: role of 5-HT1A receptors. Br J Pharmacol. 2004;142:469-78.

Rajkumar R, Mahesh R. The auspicious role of the 5-HT3 receptor in depression: a probable neuronal target? J Psychopharmacol. 2010;24:455-69.

Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology. 1999;38:1083-152.

Bétry C, Etiévant A, Oosterhof C, Ebert B, Sanchez C, Haddjeri N. Role of 5-HT3 receptors in the antidepressant response. Pharmaceuticals. 2011;4:603-29.

Yohn CN, Gergues MM, Samuels BA. The role of 5-HT receptors in depression. Mol Brain. 2017;10:28.

Poncelet M, Perio A, Simiand J, Gout G, Soubrie P, Le Fur G. Antidepressant-like effectsof SR 57227A, a 5-HT3 receptor agonist, in rodents. J Neural Transm Gen Sect. 1995;102:83-90.

Redrobe JP, Bourin M. Partial role of 5-HT2 and 5-HT3 receptors in the activity of antidepressants in the mouse forced swimming test. Eur J Pharmacol. 1997;325:129-35.

Patrick M, Richard JB, Michel H, Alain JP. Antidepressant-like action of 8-OH-DPAT, a 5-HT1A agonist, in the learned helplessness paradigm: evidence for a postsynaptic mechanism. Behav Brain Res. 1990;38:135-44.

Willner P. Validity, reliability and utility of the chronic mild stress (CMS) model of depression: A ten-year review and evaluation. (Plus 17 peer commentaries and author's response). Psychopharmacology. 1997;134:319-77.

Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl). 1985;85:367-70.

Sánchez C, Gruca P, Papp M. R-citalopram counteracts the antidepressant-like effect of escitalopram in a rat chronic mild stress model. Behav Pharmacol. 2003;14:465-70.

Nutt DJ. Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry. 2008;69:E1:4-7.

Goodnick PJ. Use of antidepressants in treatment of co-morbid diabetes mellitus and depression as well as in diabetic neuropathy. Ann Clin Psychiatry. 2001;13:31-41.

Radhakrishnan M, Viyogi S, Pandey DK, Yadav S. Evaluation of anti-depressant and analgesic-like activity of Ondansetron in a rodent model of co-morbid pain and depression. Indian J Pharm Educ Res. 2010;44.

Bourke CH, Stowe ZN, Owens MJ. Prenatal antidepressant exposure: clinical and preclinical findings. Pharmacol Rev. 2014;66:435-65.

Luscombe GP, Martin KF, Hutchins LJ, Gosden J, Heal DJ. Mediation of the antidepressant-like effect of 8-OH-DPAT in mice by postsynaptic 5-HT1A receptors. Br J Pharmacol. 1993;108:669-77.

Wieland S, Lucki I. Antidepressant-like activity of 5-HT1A agonists measured with the forced swim test. Psychopharmacology (Berl). 1990;101:497-504.

Przegaliński E, Tatarczyńska E, Kłodzińska A, Chojnacka-Wójcik E. The role of postsynaptic 5-HT1A receptors in the anticonflict effect of ipsapirone. Neuropharmacology. 1994;33:1109-15.

Qiao Y, Zhao J, Li C, Zhang M, Wei L, Zhang X, Kurskaya O, Bi H, Gao T. Effect of combined chronic predictable and unpredictable stress on depression-like symptoms in mice. Ann Transl Med. 2020;8:942.

Wang Q, Timberlake MA 2nd, Prall K., Dwivedi Y. The recent progress in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2017;77:99-109.

Muscat R, Papp M, Willner P. Reversal of stress-induced anhedonia by the atypical antidepressants, fluoxetine and maprotiline. Psychopharmacology. 1992;109:433-8.

Redrobe JP, MacSweeney CP, Bourin M. The role of 5HT1a and 5HT1b receptors in antidepressant drug actions in the mouse forced swimming test. Eur J Pharmacol. 1996;318:213-20.