phkineticaФармакокинетика и ФармакодинамикаPharmacokinetics and Pharmacodynamics2587-78362686-8830ООО «Издательство ОКИ»10.37489/2587-7836-2022-1-20-29phkinetica-305Research ArticleДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ ФАРМАКОДИНАМИКИPRECLINICAL PHARMACODYNAMICS STUDIESИзучение эффектов диазепама на асцитную карциному Эрлиха и тревожные реакции у мышей самцов популяции SHKStudy of diazepam effects on Ehrlich ascites carcinoma and anxiety responses in male SHK micehttps://orcid.org/0000-0002-0178-3567КалининаТ. С.KalininaT. S.

Татьяна Сергеевна Калинина, д. б. н., в. н. с.

лаборатория психофармакологии

Москва

Tatiana S. Kalinina, Dr. Sci. (Biol.), Leading researcher

Laboratory of psychopharmacology

Moscow

tat.calinina2009@yandex.ruhttps://orcid.org/0000-0001-6913-3248ШимширтА. А.ShimshirtA. A.

Александр Александрович Шимширт, к. б. н., н. с.

лаборатория психофармакологии

Федеральный исследовательский центр «Фундаментальные основы биотехнологии»

Москва

Alexandr A. Shimshirt, PhD Biological Sci., Researcher

Laboratory of psychopharmacology

Moscow

spring05-79@yandex.ruhttps://orcid.org/0000-0002-3922-5253ЛисицкаяК. В.LisitskayaK. V.

Ксения Валерьевна Лисицкая, к. б. н., н. с.

Федеральный исследовательский центр «Фундаментальные основы биотехнологии»

Институт биохимии имени А. Н. Баха

лаборатория биомедицинских исследований

Москва

Ksenia V. Lisitskaya, PhD Biological Sci., Researcher

Federal Research Centre “Fundamentals of Biotechnology”

Bach Institute of Biochemistry

Laboratory of biomedical research

Moscow

lisksenia@mail.ruhttps://orcid.org/0000-0003-0914-2825ВолковаА. В.VolkovaA. V.

Анна Валерьевна Волкова, н. с.

лаборатория психофармакологии

Москва

Anna V. Volkova, Researcher

Laboratory of psychopharmacology

Moscow

volk16@inbox.ruhttps://orcid.org/0000-0002-1819-1867КудряшовН. В.KudryashovN. V.

Никита Викторович Кудряшов, к. б. н., с. н. с.

Федеральное государственное автономное образовательное учреждение высшего образования Первый Московский государственный медицинский университет имени И. М. Сеченова (Сеченовский Университет)

лаборатория психофармакологии

Москва

Nikita V. Kudryashov, PhD Biological Sci., Senior researcher

Federal State Autonomous Educational Institution of Higher Education I. M. Sechenov First Moscow State Medical University (Sechenovskiy University)

Laboratory of psychopharmacology

Moscow

kunvi@mail.ruФГБНУ «НИИ фармакологии имени В. В. Закусова»РоссияFSBI “Zakusov Institute of Pharmacology”Russian FederationРАНРоссияRussian Academy of SciencesRussian FederationФГБНУ «НИИ фармакологии имени В. В. Закусова»; Министерство здравоохранения Российской ФедерацииРоссияFSBI “Zakusov Institute of Pharmacology”; Ministry of Healthcare of the Russian FederationRussian Federation202201052022012029Copyright © Калинина Т.С., Шимширт А.А., Лисицкая К.В., Волкова А.В., Кудряшов Н.В., 20222022Калинина Т.С., Шимширт А.А., Лисицкая К.В., Волкова А.В., Кудряшов Н.В.Kalinina T.S., Shimshirt A.A., Lisitskaya K.V., Volkova A.V., Kudryashov N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacokinetica.ru/jour/article/view/305

   Актуальной проблемой является коморбидность злокачественных опухолей и аффективных расстройств. Известно о неблагоприятном влиянии некоторых психотропных лекарственных средств на злокачественные опухоли и метастазирование, в эксперименте установлена связь нейромедиаторов с опухолями. Известно свойство диазепамa стимулировать рост асцитной карциномы Эрлиха в эксперименте на мышах.

   Целью настоящего исследования явилось изучение роли бензодиазепиновых рецепторных сайтов разной локализации в стимулирующем влиянии диазепама на карциному Эрлиха. При использовании фармакологических анализаторов бензодиазепинового сайта центрального ГАМКА рецептора флумазенила (5 мг/кг, подкожно) и блокатора митохондриального транспортного белка 18 кДа соединения PK11195 (5 мг/кг, подкожно) были изучены эффекты диазепама (0,03 и 3,0 мг/кг, интрагастрально) на развитие асцитной карциномы Эрлиха и ориентировочно-исследовательскую реакцию в тесте «открытое поле» на мышах самцах популяции SHK. Установлено, что диазепам в дозе 0,03 мг/кг, но не в дозе 3 мг/кг, увеличивает клеточность опухолевого выпота. Вместе с тем, диазепам в обеих изученных дозах вызывает увеличение периферической двигательной активности у мышей, что указывает на усиление тревожных реакций. Установлено, что флумазенил, но не PK11195, ослабляет стимулирующий эффект диазепама на асцитную карциному Эрлиха и ингибирует про-анксиогенное действие малой дозы диазепама. Полученные результаты позволяют сделать вывод об отсутствии ассоциативной связи между проопухолевым действием диазепама и его влиянием на тревожные реакции, но при этом не исключать участие центральных механизмов в стимулирующем эффекте низких доз бензодиазепина на опухоль.

   Сomorbidity of malignant tumors and affective disorders is an urgent problem. It is known that some psychotropic drugs may adversely influence the growth of malignant tumors and metastasis; in the experiment, a connection between neurotransmitters and tumors was established. Earlier, in experiments on mice, the ability of diazepam to stimulate the growth of Ehrlich's ascites carcinoma was demonstrated.

   The aim of this study was to assess the role of central and peripheral benzodiazepine receptor sites in the stimulating effect of diazepam on Ehrlich's carcinoma. The effects of diazepam (0.03 and 3.0 mg / kg, intragastric) on the development of Ehrlich's ascites carcinoma and an orientation-exploratory response in the "open field" test on male SHK mice were studied. It was found that diazepam at a dose of 0.03 mg / kg, but not at a dose of 3 mg / kg, increases the cellularity of the malignant ascites. At the same time, diazepam in both doses studied causes an increase in the peripheral motor activity of mice, which indicates an increase in anxiety reactions. It was found that flumazenil, but not PK11195, attenuates the stimulating effect of diazepam on Ehrlich's ascites carcinoma and inhibits the pro-anxiogenic effect of a small dose of diazepam. The results obtained allow us to conclude that there is no associative relationship between the pro-tumor effect of diazepam and its effect on anxiety responses, but at the same time, the participation of central mechanisms in the stimulating effect of benzodiazepine on the tumor cannot be ruled out.

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The authors declare that there are no conflicts of interest present.