Актуальность

phkinetica

Фармакокинетика и Фармакодинамика

Pharmacokinetics and Pharmacodynamics

2587-78362686-8830

ООО «Издательство ОКИ»

10.37489/2587-7836-2024-2-34-42

HLEVUO

phkinetica-417

Research Article

ДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ ФАРМАКОДИНАМИКИ

PRECLINICAL PHARMACODYNAMICS STUDIES

Особенности поведения крыс Вистар на моделях расстройств аутистического спектра, вызванных пренатальным или постнатальным введением вальпроата натрия

Behavioral features of Wistar rats in models of autism spectrum disorders induced by prenatal or postnatal administration of sodium valproate

https://orcid.org/0009-0007-7876-5977

Савинкова

Е. В.

Savinkova

E. V.

Савинкова Елена Владимировна, д. б. н., в. н. с. лаборатории фармакокинетики

Москва

Elena V. Savinkova, PhD, Dr. Sci. (Biology), Leading Researcher of Laboratory of Pharmacokinetics

Moscow

savinkova_ev@academpharm.ru

https://orcid.org/0000-0003-4487-0991

Капица

И. Г.

Kapitsa

I. G.

Капица Инга Геннадиевна, к. б. н., в. н. с., начальник отдела интеллектуальной собственности

Москва

Inga G. Kapitsa, PhD, Cand. Sci. (Biology), Leading Researcher, Head of the Intellectual Property Department

Moscow

https://orcid.org/0000-0001-7065-469X

Воронина

Т. А.

Voronina

T. A.

Воронина Татьяна Александровна, д. м. н., профессор, г. н. с., руководитель отдела нейропсихофармакологии, заведующий лабораторией фармакологии психических заболеваний

Москва

Tatiana A. Voronina, PhD, Dr. Sci. (Med.), professor, Chief Scientific Officer, Head of the Department of Neuropsychopharmacology, Head of the Laboratory of Pharmacology of Mental Diseases

Moscow

ФГБНУ «ФИЦ оригинальных и перспективных биомедицинских и фармацевтических технологий»РоссияFederal research center for innovator and emerging biomedical and pharmaceutical technologiesRussian Federation

2024

08082024

023442

2024

Савинкова Е.В., Капица И.Г., Воронина Т.А.

Savinkova E.V., Kapitsa I.G., Voronina T.A.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.pharmacokinetica.ru/jour/article/view/417

Актуальность

Актуальность. Сложности диагностики и лечения расстройств аутистического спектра (РАС) обусловлены их неизвестной этиологией и патофизиологией. Изучение моделей РАС, вызванных воздействием вальпроата натрия (ВН), имеет важное значение для разработки эффективной фармакологической коррекции этого расстройства.

Цель

Цель. Целью исследования являлась оценка влияния пренатального и постнатального воздействия ВН на развитие аутичноподобного поведения у крыс линии Вистар для дальнейшего выбора целесообразного терапевтического воздействия.

Методы

Методы. Потомство крыс линии Вистар получали ВН на 12,5-й день пренатального развития или постнатально на 14-й день. Проводили оценку социального поведения, тревожности, рабочей памяти, оборонительного видового поведения, исследовательской и двигательной активности.

Результаты

Результаты. Пренатальное воздействие ВН привело к снижению социального взаимодействия, повышению тревожности, нарушению видового оборонительного поведения и уменьшению двигательной активности у самцов крыс. У самок крыс с ВН, введённым пренатально, отмечались социальный дефицит, повышение тревожности и гиполокомоция, а также нарушения в когнитивной сфере, но не предпочтение к аверсивному запаху. ри постнатальном воздействии ВН на самцов и самок крыс не наблюдалось существенных изменений в социальном взаимодействии и видовом оборонительном поведении, однако животные показали снижение двигательной активности. У самок, получавших ВН постнатально, отмечалось ухудшение рабочей памяти и снижение исследовательского поведения.

Заключение

Заключение. Как пренатальное, так и постнатальное воздействие ВН вызывает нарушения поведения, сходные с РАС, и имеет гендерные особенности, что может определить направление фармакологической коррекции заболевания.

Relevance

Relevance. The complexity of diagnosing and treating autism spectrum disorders (ASD) is attributed to their unknown etiology and pathophysiology. The investigation of ASD models induced by sodium valproate (VPA) holds significant importance in the development of effective pharmacological interventions for this disorder.

Objective

Objective. The aim of the study was to assess the impact of prenatal and postnatal exposure to VPA on the development of autism-like behavior in Wistar rats for further selection of appropriate therapeutic interventions.

Methods

Methods. Offspring of Wistar rats were exposed to VPA on the 12.5th day of prenatal development or postnatally on the 14th day. Evaluation included assessment of social behavior, anxiety, working memory, species-typical defensive behavior, exploratory, and locomotor activity.

Results

Results. Prenatal VPA exposure led to reduced social interaction, increased anxiety, disruption of species-typical defensive behavior, and decreased locomotor activity in male rats. Female rats prenatally exposed to VPA exhibited social deficits, increased anxiety, hypolocomotion, and cognitive impairments, albeit without displaying aversive odor preference. Postnatal VPA exposure in male and female rats did not significantly alter social interaction and species-typical defensive behavior; however, animals exhibited reduced locomotor activity. Postnatally VPA-exposed female rats demonstrated worsened working memory and decreased exploratory behavior.

Conclusion

Conclusion. Both prenatal and postnatal exposure to VPA elicits behavioral disturbances resembling ASD, with gender-specific nuances, which may guide the direction of pharmacological interventions for the disorder.

расстройства аутистического спектрафетальный вальпроатный синдромпренатальное воздействие вальпроата натриякрысы линии Вистарсоциальное взаимодействиетревожностьаверсивный запахкогнитивные функцииисследовательское поведениедвигательная активность

autism spectrum disordersfetal valproate syndromepostnatal valproateWistar ratssocial interactionanxietyaversive odorcognitive functionsexploratory behaviorlocomotor activity

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