Psychopharmacology and Addiction BiologyPsychopharmacology and Addiction BiologyПсихофармакология и биологическая наркология1606-81812070-5670Eco-Vector62741110.17816/phbn627411NeuropsychopharmacologyПсихонейрофармакологияResearch ArticleSedative effect of U-49900 (3,4-dichloro-N- (2-(diethylamino)cyclohexyl)-N-methyl-benzamide) in adult ZebrafishСедативный эффект U-49900 (3,4-дихлор-N- (2-(диэтиламино)циклогексил)-N-метил-бензамида) на взрослых рыбах зебраданиоhttps://orcid.org/0000-0002-5561-85838558-7887KolesnikovaT. O.КолесниковаТ. О.
Russian Federation
Philimontani@yandex.ruhttps://orcid.org/0000-0002-0369-07865899-6920ShevyrinV. A.ШевыринВ. А.
Russian Federation

Cand. Sci. (Biology)

канд. биол. наук

vadim.shevyrin@gmail.comhttps://orcid.org/0000-0001-5921-66804973-7083KhatskoS. L.ХацкоС. Л.
Russian Federation
hardscore@mail.ruhttps://orcid.org/0000-0002-7525-19504134-0515KalueffA. V.КалуевА. В.
Russian Federation

Dr. Sci. (Biology)

д-р биол. наук

avkalueff@gmail.comSirius University of Science and TechnologyНаучно-технологический университет «Сириус»Ural Federal UniversityУральский федеральный университетAlmazov National Medical Research CenterНациональный медицинский исследовательский центр им. В.А. Алмазова12042024170620241521271342402202412042024Copyright ©; 2024, Eco-VectorCopyright ©; 2024, Эко-Вектор2024Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0https://journals.eco-vector.com/1606-8181/article/view/627411

BACKGROUND: U-49900 is a chemical analog of U-47700. Despite the growing abuse of synthetic opioids, including U-49900, its psychopharmacological and toxicological profiles remain poorly understood. The zebrafish (Danio rerio) is a promising model organism in neuroscience often used for the psychopharmacological evaluation of neurotropic drugs. OBJECTIVE: To evaluate the effects of U-49900 on the behavior of adult zebrafish in a new tank. MATERIALS AND METHODS: The effect of the test compound U-49900 at 1, 5, 10, and 25 mg/L concentrations (incubation for 20 minutes) on the behavior of adult zebrafish was assessed using the “new aquarium” test. U-49900 is 3.4-dichloro-N-(2-(diethylamino)cyclohexyl)-N-methylbenzamide and is considered an analog of the synthetic opioid U-47700, causing withdrawal in humans. RESULTS: The psychopharmacological profile of U-49900 at 1, 5, 10, and 25 mg/l concentrations (water immersion) in adult zebrafish was evaluated with the novel tank test. U-49900 at 25 mg/l for 20 min reduced the distance traveled and number of top entries in the novel tank test (p < 0.001 vs. control group), but unaltered other parameters. CONCLUSIONS: Overall, the sensitivity of zebrafish to synthetic non-fentanyl opioids such as U-49900 indicates the possibility of developing high-throughput screening platforms for finding effective therapies for pathological conditions caused by synthetic opioids.

Обоснование. U-49900 — химический аналог селективного агониста μ-опиоидных рецепторов U-47700 c выраженными психоактивными свойствами. Несмотря на рост злоупотреблений синтетическими опиоидами, в том числе U-47700 и U-49900, психофармакологический профиль последнего изучен мало. Костная рыба зебраданио (zebrafish, Danio rerio) представляет перспективный акватический модельный организм в нейробиологии и широко используется для психофармакологического анализа свойств нейротропных препаратов. Цель — оценить эффекты U-49900 на поведение взрослых зебраданио в тесте «нового аквариума». Материалы и методы. Оценивали действие соединения U-49900 в концентрации 1, 5, 10 и 25 мг/л (инкубация в течение 20 мин) на поведение взрослых зебраданио в тесте «нового аквариума». U-49900 — 3,4-дихлор-N-(2-(диэтиламино)циклогексил)-N-метилбензамид, аналог синтетического опиоида U-47700, вызывает у человека абстиненцию. Результаты и обсуждение. В концентрации 25 мг/л U-49900 уменьшает пройденную дистанцию и количество выходов в верхнюю часть аквариума в тесте «нового аквариума» (р < 0,001 по сравнению с контрольной группой), но не изменяет другие параметры в тесте. Данный профиль согласуется с выраженным седативным действием препарата. Заключение. В целом чувствительность зебраданио к U-49900 предполагает возможность разработки высокопроизводительных платформ для скрининга препаратов и их мишеней с целью поиска эффективной терапии патологических состояний, вызванных синтетическими опиоидами.

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