vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ16.135vavilov-584Research ArticleЭкспрессия ключевых генов физиологических функций. ОБЗОРExpression of genes crucial for physiological functions. REVIEW5-HT1А рецептор: роль в регуляции различных видов поведения5-HT1A receptor: its role in the regulation of different kinds of behaviorНауменкоВ. С.NaumenkoV. S.naumenko2002@bionet.nsc.ruПонимаскинЕ. Г.PonimaskinE. G.ПоповаН. К.PopovaN. K.Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, РоссияРоссияInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaRussian FederationИнститут клеточной нейрофизиологии, Высшая медицинская школа Ганновера, Ганновер, ГерманияРоссияInstitute of Cellular Neurophysiology, Hannover Medical High School, Hannover, GermanyRussian Federation201618052016202180190Copyright © Науменко В.С., Понимаскин Е.Г., Попова Н.К., 20162016Науменко В.С., Понимаскин Е.Г., Попова Н.К.Naumenko V.S., Ponimaskin E.G., Popova N.K.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/584

Нейромедиатор мозга серотонин регулирует различные формы как нормального, так и патологического поведения, действуя на 14 типов серотониновых (5-НТ) рецепторов. Все 5-НТ рецепторы, за исключением 5-НТ3, представляющего ионный канал (ионотропный рецептор), принадлежат к суперсемейству метаботропных рецепторов, сопряженных с G- белками. Каждый из типов и подтипов рецепторов характеризуется уникальным контролирующим геном, спектром сродства к разнообразным агонистам и антагонистам серотонина, специфическим распределением в мозге и рядом регулируемых функций. Среди этого многообразия 5-НТ рецепторов особый интерес вызывает эволюционно наиболее древний 5-НТ1А рецептор, играющий ключевую роль в ауторегуляции серотониновой системы мозга. Эта роль 5-НТ1А рецепторов обусловлена особенностями их локализации (пост- или пресинаптически на 5-НТ нейронах), в зависимости от которой они могут оказывать прямо противоположное действие на функциональную активность 5-НТ системы. Обзор посвящен данным литературы и результатам, полученным авторами, о факторах, регулирующих экспрессию и функциональную активность 5-НТ1А рецепторов, и их влиянии на поведение. Описана структура гена 5-НТ1А рецептора, приведены новейшие данные о посттрансляционной регуляции активности 5-НТ1А рецепторов и взаимодействии 5-НТ рецепторов. Особое внимание уделено роли гетеромеризации 5-НТ1А рецептора при его взаимодействии с 5-НТ7 серотониновым рецептором с образованием гетеродимера и функциональной инактивации 5-НТ1А рецептора. Показано участие 5-НТ1А рецепторов в регуляции агрессивного поведения, каталепсии, тревожности, депрессии и уникальной природной адаптации – зимней спячки. Особое внимание уделено участию этих рецепторов в регуляции 1) вызванной страхом защитно-оборонительной агрессии по отношению к человеку – основы процесса доместикации; 2) межсамцовой (intermale) агрессии по отношению к сопернику (конкуренту), приводящей к установлению отношения доминант – субординант в сообществе животных и лежащей в основе асоциального поведения человека; 3) механизмов депрессии и действия клинически эффективных антидепрессантов группы ингибиторов обратного захвата серотонина. Выдвинута гипотеза о роли 5-НТ1А / 5-НТ7 гетеродимеризации в механизме действия антидепрессантов.

Brain serotonin (5-HT) is known to be involved in the control of a wide range of physiological functions as well as of different kinds of behavior. Such polyfunctionality of 5-HT is mediated by numerous 5-HT receptors. Currently, 14 different 5-HT receptor subtypes expressed in the mammals have been identified. The 5-HT1А receptor is one of the most extensively characterised members of the serotonin receptor family. Increased interest to the 5-HT1А receptor is based on (1) a key role in the autoregulation of the brain serotonergic system due to the postsynaptic and presynaptic localization, (2) a great body of data demonstrating implication of 5-HT1А receptor in the control of various physiological functions (3) involvement of 5-HT1А receptors in the mechanisms of depression, anxiety and suicide. The review describes literature and original data on factors affecting the expression and functional activity of 5-HT1А receptors and the involvement of 5-HT1А receptors in the regulation of normal and pathological behavior. The structure of the 5-HT1А receptor gene is described and new data on the posttranslational regulation of 5-HT1А receptor functional activity are provided. A special focus was given to the interaction between 5-HT1А and 5-HT7 receptors followed by heterodimer formation and the role of heterodimerization in the functional inactivation of the 5-HT1А receptor. The implication of 5-HT1А receptors in the regulation of aggressive behavior, catalepsy, anxiety, depression and hibernation was shown. Special attention is focused on the involvement of 5-HT1А receptors in the regulation of 1) fear-induced aggression towards man – the basis of domestication, 2) intermale aggression underling asocial behavior in men, 3) depression and in the mechanism of antidepressant action. The described data extend the idea on the 5-HT1А receptor as a key player in the brain 5-HT system.

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