The resident-intruder model: a platform for in-depth study of novel molecules with antidepressant activity

Авторы

  • Ирина Л. Никитина Башкирский государственный медицинский университет ORCID logo https://orcid.org/0000-0002-6283-5762
  • Гульнара Г. Гаишина Башкирский государственный медицинский университет ORCID logo https://orcid.org/0000-0002-1936-3720
  • Елена Е. Клен Башкирский государственный медицинский университет ORCID logo https://orcid.org/0000-0001-7538-6030
  • Екатерина А. Маракаева Башкирский государственный медицинский университет
  • Екатерина А. Никитина Федеральный научно-исследовательский центр инновационных и перспективных биомедицинских и фармацевтических технологий ORCID logo https://orcid.org/0000-0002-0400-3749
  • Николай А. Костин Санкт-Петербургский университет
  • Ксения Н. Федосеева Санкт-Петербургский университет
  • Любовь А. Ткаченко Санкт-Петербургский университет ORCID logo https://orcid.org/0000-0002-9051-9636

DOI:

https://doi.org/10.18413/rrpharmacology.11.646

Аннотация

Introduction: The aim of the study was to investigate the features of the resident-intruder paradigm as a basic translational method for in-depth evaluation of antidepressant activity of new compounds using the example of 3-ethoxythietane-1,1-dioxide (3ETD), which has antidepressant activity.

Materials and Methods: A depressive-like state in white non-inbred rats (intruders) was modeled by long-term (24-day) exposure to chronic social stress (CSS) during interaction with residents. Intruders were divided into 4 experimental groups (n=6). Intruders of the CSS and CSS+3ETD groups interacted with residents daily for 10 min from Day 0 to Day +23, 30 min after intraperitoneal administration of 3ETD (2 mg/kg, 3ETD, CSS+3ETD groups) or saline (Vehicle and CSS groups). At the end of the experiment, the behavior of intruders of all groups was studied in the forced swimming test (FST, Day +23), open field test, and elevated plus maze test (Day +24). Intruders’ body weight and food consumption were measured daily. After euthanasia (Day +24), the weight coefficients of internal organs were calculated and the level of apoptosis markers/regulators in the rat hippocampus was determined immunohistochemically.

Results and Discussion: CSS induced a state similar to asthenic depression in intruders: it increased immobility time in FST, the duration of passive behaviors (including submissive), while the duration of active behaviors (defensive, exploratory, social) decreased. 3ETD eliminated these manifestations, exerting an antidepressant effect: it reduced the despair behavior in FST, enhanced motor activity, social and exploratory behavior of intruders, stimulated active defense and reduced passive defense during contact with residents, as well as reduced apoptosis in the hippocampus of intruders, exhibiting neuroprotective properties.

Conclusion: The resident-intruder model allows modeling in rats a condition similar to the human asthenic depression and demonstrating the antidepressant effect of novel molecules, as was shown on the 3ETD example when administered at a dose of 2 mg/kg/day intraperitoneally.

Графическая аннотация

Ключевые слова:

antidepressant activity, resident-intruder, animal outbred strain, thietane

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Вклад авторов

Ирина Л. Никитина, Башкирский государственный медицинский университет

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.

Гульнара Г. Гаишина, Башкирский государственный медицинский университет

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.

Елена Е. Клен, Башкирский государственный медицинский университет

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.

Екатерина А. Маракаева, Башкирский государственный медицинский университет

Assistant Professor of the Department of Pharmacology, Bashkir State Medical University; junior researcher at the Laboratory of Search for Small Target Molecules, Bashkir State Medical University, Ufa, Russia; e-mail: katrin87victory@yandex.ru. The author took part in experimental work and prepared the final version of the article.

Екатерина А. Никитина, Федеральный научно-исследовательский центр инновационных и перспективных биомедицинских и фармацевтических технологий

Junior researcher of the Department of Neuropsychopharmacology, Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies; researcher at the Laboratory of Pharmacology of Neurological Diseases, Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow, Russia; e-mail: nikitina_ea@academpharm.ru; ORCID ID: https://orcid.org/0000-0002-0400-3749. The author took part in experimental work and prepared the final version of the article.

Николай А. Костин, Санкт-Петербургский университет

Specialist of Research Resource Center for Molecular and Cell Technologies, St. Petersburg State University, St. Petersburg, Russia; e-mail: kostin@spbu.ru. The author performed histological and immunohistochemical analysis and prepared the final version of the article.

Ксения Н. Федосеева, Санкт-Петербургский университет

Deputy Director of Research Resource Center for Molecular and Cell Technologies, St. Petersburg State University, St. Petersburg, Russia; e-mail: fedoseeva@spbu.ru. The author performed histological and immunohistochemical analysis and prepared the final version of the article.

Любовь А. Ткаченко, Санкт-Петербургский университет

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.

Загрузки

Опубликован

18.12.2025

Как цитировать

Nikitina IL, Gaisina GG, Klen EE, Marakaeva EA, Nikitina EA, Kostin NA, Fedoseeva KN, Tkachenko LA (2025) The resident-intruder model: a platform for in-depth study of novel molecules with antidepressant activity. Research Results in Pharmacology 11(4): 102–112. https://doi.org/10.18413/rrpharmacology.11.646

Выпуск

Том 11 № 4 (2025)

Раздел

Экспериментальная фармакология

Лицензия

Copyright (c) 2025 Nikitina1 IL, Gaisina GG, Klen EE, Marakaeva EA, Nikitina EA, Kostin NA, Fedoseeva KN, Tkachenko LA

Лицензия Creative Commons

Это произведение доступно по лицензии Creative Commons «Attribution» («Атрибуция») 4.0 Всемирная.

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