uzspbgmuУчёные записки Первого Санкт-Петербургского государственного медицинского университета имени академика И. П. ПавловаThe Scientific Notes of the Pavlov University1607-41812541-8807Academician I.P. Pavlov First St. Petersburg State Medical University10.24884/1607-4181-2022-29-3-31-39uzspbgmu-911Research ArticleОРИГИНАЛЬНЫЕ РАБОТЫORIGINAL PAPERSВлияние блокады глутаматных рецепторов NMDA-подтипа в неонатальный период на поведение взрослых самцов крысEffects of neonatal NMDA-subtype glutamate receptor blockade on behavior of adult male ratshttps://orcid.org/0000-0001-9251-9923СухановИ. М.SukhanovI. M.

доктор медицинских наук, зав. лабораторией фармакологии поведения отдела психофармакологии Института фармакологии им. А. В. Вальдмана, 

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

Dr. of Sci. (Med.), Head of the Laboratory of Behavioral Pharmacology of the Department of Psychopharmacology of Valdman Institute of Pharmacology, 

6-8, L’va Tolstogo str., Saint Petersburg, 197022

ilia.sukhanov@gmail.comhttps://orcid.org/0000-0001-7100-7857ДраволинаО. А.DravolinaO. A.

кандидат биологических наук, зав. лабораторией экспериментальной фармакологии аддиктивных состояний отдела психофармакологии Института фармакологии им. А. В. Вальдмана, 

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

Cand. of Sci. (Biol.), Head of the Laboratory of Experimental Pharmacology of Addictive States of the Department of Psychopharmacology of Valdman Institute of Pharmacology, 

6-8, L’va Tolstogo str., Saint Petersburg, 197022

olga.dravolina@gmail.comhttps://orcid.org/0000-0001-8572-3600БелозерцеваИ. В.BelozertsevaI. V.

кандидат биологических наук, зав. отделом психофармакологии Института фармакологии им. А. В. Вальдмана,

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

Cand. of Sci. (Biol.), Head of the Department of Psychopharmacology of Valdman Institute of Pharmacology, 

6-8, L’va Tolstogo str., Saint Petersburg, 197022

belozertseva@gmail.comhttps://orcid.org/0000-0001-7056-0925СухотинаИ. А.SukhotinaI. A.

кандидат биологических наук, доцент кафедры фармакологии, 

197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8

Cand. of Sci. (Biol.), Associate Professor of the Department of Pharmacology, 

6-8, L’va Tolstogo str., Saint Petersburg, 197022

irina.sukhotina@gmail.comФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияPavlov UniversityRussian Federation2022230720222933139Copyright © Суханов И.М., Драволина О.А., Белозерцева И.В., Сухотина И.А., 20222022Суханов И.М., Драволина О.А., Белозерцева И.В., Сухотина И.А.Sukhanov I.M., Dravolina O.A., Belozertseva I.V., Sukhotina I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sci-notes.ru/jour/article/view/911Введение

Введение. Когнитивные нарушения – важная составляющая клинической картины многих нейропсихических расстройств, к коррекции которых отсутствуют доказанно-эффективные фармакотерапевтические подходы.

Цель работы – апробация модели отсроченных когнитивных нарушений вследствие введения антагонистов глутаматных рецепторов NMDA-подтипа в неонатальный период жизни крыс (7-й, 9-й и 11-й дни жизни).

Методы и материалы

Методы и материалы. Самцам крыс Wistar неонатально вводили фенциклидин, 10 мг/кг (эксперимент 1), или (+) MK-801, 1 мг/кг (эксперимент 2). Оценивали поведение взрослых крыс в «двухпедальном тесте оценки внимания» и «тесте оценки адаптации поведения к смене режима пищевого подкрепления» соответственно.

Результаты

Результаты. Эксперимент 1: крысы экспериментальной группы аккуратнее выполняли задачу и совершали меньше пропусков попыток по сравнению с контролем. Эксперимент 2: изменение режима подкрепления приводило к увеличению паузы после подкрепления в обеих группах; в экспериментальной группе длительность паузы после подкрепления была меньше.

Заключение

Заключение. Неонатальная блокада глутаматных рецепторов NMDA-подтипа приводит к развитию отсроченных нарушений ингибиторного контроля и внимания к сенсорному стимулу, что проявляется, соответственно, как повышение импульсивности и гиперфокусировка в условиях ограниченного выбора. 

Introduction

Introduction. Cognitive impairments are important components of the clinical picture of many neuropsychiatric disorders, and are in dire need of evidence-based pharmacotherapeutic approaches.

The objective was to test a model of delayed cognitive impairments due to neonatal administration of NMDA receptor antagonists (7th, 9 th, and 11 th days of life).

Methods and materials

Methods and materials. Male Wistar rats were administered with phencyclidine, 10 mg/kg (Experiment 1), or (+)MK-801, 1 mg/kg (Experiment 2); then «2-choice serial reaction time task», or «reinforcement learning task based on response patterning under interval schedules of reinforcement» in the same adult rats were performed.

Results

Results. Experiment 1: rats after neonatal NMDA-blockade performed operant tasks more accurately and made fewer missed attempts as compared to control. Experiment 2: switching to another schedule of reinforcement increased the pause after reinforced responses in both groups; in the experimental group, the duration of the post-reinforcement pause was shorter.

Conclusion

Conclusion. Neonatal NMDA receptor blockade affects inhibitory control and attention to sensory stimuli, which manifests, respectively, as increased impulsivity and hyperfocusing in limited-choice conditions. 

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