Assessment of the 3-substituted thietane-1,1-dioxide derivative antidepressant effect using rat model of depression induced by reserpine

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.11.542

Abstract

Introduction: 3-ethoxythietane-1,1-dioxide (3ETD) is a novel molecule that has demonstrated significant antidepressant properties when administered intraperitoneally (i.p.) to mice once or repeatedly. The aim of the study was to evaluate the antidepressant effect of 3ETD in a model of depressive-like state in rats induced by seven-fold administration of reserpine.

Materials and Methods: We conducted two sets of experiments in white outbred male rats. In Experiment 1, reserpine(0.5 mg/kg) was administered intraperitoneally daily from Day 0 to Day +6; 3ETD (2 mg/kg) and the reference drug amitriptyline (10 mg/kg) were administered i.p. daily from Day 0 to Day +11. The sucrose intake and preference (Days 0, +6, +12), the coat state (Days 0, +6, +12), the behavior of the rats in the forced swimming test (FST, +12 day), the open field test (OF, Day +13) and the elevated plus maze test (EPM, Day +13), as well as the body weight (daily) were assessed. On Day +13, the animals were sacrificed and the weight coefficients of their internal organs (liver, spleen, thymus, adrenal glands) were measured and serum chemistry was performed. Brain-derived neurotrophic factor (BDNF) level in the hippocampus was quantified by enzyme-linked immunosorbent assay (ELISA). In Experiment 2, reserpine, amitriptyline, and 3 ETD were administered similarly to Experiment 1, and on Day +13, rats were euthanized and brain samples were collected for immunohistochemical determination of glial fibrillary acidic protein (GFAP) and anti-apoptotic B-cell lymphoma-2 protein (Bcl-2) in the hippocampus.

Results and Discussion: Seven-fold administration of reserpine significantly increased immobility time (IT) in FST, caused anhedonia and coat state deterioration, decreased motor activity in OF and EPM, decreased body weight, increased the adrenal glands and spleen weight coefficients, increased GFAP level and decreased Bcl-2 level in the hippocampus. 3ETD (2 mg/kg) significantly reduced IT FST by 39%, increased sucrose preference to the level of the control group and sucrose consumption by 137%, eliminated self-care deficit, prevented weight loss in rats by the end of the experiment (Experiment 1); significantly reduced GFAP level (CA1-CA4, dentate gyrus) and increased Bcl-2 level (CA1, dentate gyrus) in the hippocampus compared with the reserpine group (Experiment 2).

Conclusion: 3ETD eliminated depressive-like symptoms in rats induced by seven-fold administration of reserpine.

Graphical Abstract

Keywords:

thietane, antidepressive agents, rats, reserpine, depression

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Author Contribution

Irina L. Nikitina, Bashkir State Medical Univercity

Doctor Habil. of Medical Sciences, Professor of the Department of Pharmacology, Bashkir State Medical University; senior researcher at the Laboratory of Search for Small Target Molecules, Bashkir State Medical University, Ufa, Russia; e-mail: irennixleo@gmail.com, ORCID ID: https://orcid.org/0000-0002-6283-5762. The author developed the idea, concept and design of the study, supervised the planning and conduct of research activities, analyzed the results and edited the final version of the article.

Gulnara G. Gaisina, Bashkir State Medical University

Candidate of Medical Sciences, Associate Professor of the Department of Pharmacology, Bashkir State Medical University; researcher at the Laboratory of Search for Small Target Molecules, Bashkir State Medical University, Ufa, Russia; e-mail: gugaisy@gmail.com, ORCID ID: https://orcid.org/0000-0002-1936-3720. The author took part in experimental work, performed statistical analysis and prepared the final version of the article.

Elena E. Klen, Bashkir State Medical University

Doctor Habil. of Pharmaceutical Sciences, Professor, Head of the Department of Pharmaceutical, Analytical and Toxicological Chemistry, Bashkir State Medical University; senior researcher at the Laboratory of Search for Small Target Molecules, Bashkir State Medical University, Ufa, Russia; e-mail: klen_elena@yahoo.com, ORCID ID:https://orcid.org/0000-0001-7538-6030. The author synthesized the compound and prepared the final version of the article.

Lyubov A. Tkachenko, St. Petersburg State University

Candidate of Biological Sciences, Associate Professor of Department of Cytology and Histology, St. Petersburg State University, St. Petersburg, Russia; e-mail: lyubovtkachenko@gmail.com, ORCID ID: https://orcid.org/0000-0002-9051-9636. The author performed histological and immunohistochemical analysis and prepared the final version of the article.

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Published

28-03-2025

How to Cite

Nikitina IL, Gaisina GG, Klen EE, Tkachenko LA (2025) Assessment of the 3-substituted thietane-1,1-dioxide derivative antidepressant effect using rat model of depression induced by reserpine. Research Results in Pharmacology 11(1): 13–26. https://doi.org/10.18413/rrpharmacology.11.542

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Section

Experimental Pharmacology