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Original Research Article | OPEN ACCESS

Comparative effect of fluoxetine and imipramine on anxiety-like phenotypes in social defeat stress model in mice

Festus E Avwotuhwaye1, 2 , Anthony T Eduviere1, Celestine O Akpovwre1, Michael A Kadiri2, Winifred E Demaki1, Akinsola A Olubiyi3, Israel O Efejene4

1Department of Pharmacology, Faculty of Applied health Sciences, College of Health Sciences, Delta State University, Abraka, Delta State; 2Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Medical Science, Edo University, Iyamho, Edo State; 3Department of Physiology (Pharmacology unit), Faculty of Basic Medical Sciences, Redeemer’s University, Ede, Osun State; 4Department of Pharmacology, Faculty of Basic Medical Sciences, Southern Delta University, Ozoro, Delta State, Nigeria.

For correspondence:-  Festus Avwotuhwaye   Email: a.festus1992@gmail.com   Tel:07067564506

Received: 2 June 2025        Accepted: 18 November 2025        Published: 30 November 2025

Citation: Avwotuhwaye FE, Eduviere AT, Akpovwre CO, Kadiri MA, Demaki WE, Olubiyi AA, et al. Comparative effect of fluoxetine and imipramine on anxiety-like phenotypes in social defeat stress model in mice. Trop J Pharm Res 2025; 24(11):1357-1369 doi: https://dx.doi.org/10.4314/tjpr.v24i11.4

© 2025 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To evaluate the comparative effect of fluoxetine and imipramine on socially defeated mice. Methods: Twenty-eight mice were divided into four groups of seven each as follows: 1 - Control (distilled water), 2 - untreated social defeat stress (SDS), 3 - SDS + fluoxetine (10 mg/kg), and 4 - SDS + imipramine (10 mg/kg. Anxiety was created via social defeat stress for 30 days; thereafter, animals were treated orally with fluoxetine (10 mg/kg) and imipramine (10 mg/kg) for 14 consecutive days. Twenty-four hours after the last administration, different behavioural tests, including elevated plus maze test and light and dark box test, were conducted, after which the animals were sacrificed by decapitation and brain regions (prefrontal cortex, dentate gyrus, amygdala and striatum were obtained for analysis (superoxide dismutase, brain-derived neurotropic factor, interleukin-10 and interleukin-1alpha. Results: Fluoxetine displayed a stronger anxiolytic effect in the elevated plus maze test and time spent in the dark box compared to imipramine (p < 0.05). Both treatment groups seem to have an equivalent effect on superoxide dismutase (SOD) and malondialdehyde (MDA) levels in both the prefrontal cortex and hippocampus. Neuronal density counts in the hippocampus (dentate gyrus), striatum, and amygdala exhibited a mirror effect for both treated groups. Imipramine boosted levels of interleukin-10 considerably (p < 0.05) compared to fluoxetine, but both drugs showed equivalent effect on brain-derived neurotropic factor, nuclear factor kappa-B, and interleukin-1 alpha. Conclusion: Although both drugs utilized for the study are antidepressants, outcomes from this study have demonstrated that both drugs have anti-anxiety-like effects, with fluoxetine displaying a better effect. However, both treatment groups (imipramine and fluoxetine) had equivalent effects in most of the studies undertaken.

Keywords: Anxiety, Social defeat stress, Fluoxetine, Imipramine

Impact Factor
Thompson Reuters (ISI): 0.6 (2023)
H-5 index (Google Scholar): 49 (2023)

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