Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences68741410.31857/S0869813925060083TEQXKSEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИResearch ArticleThe Role of GABA Receptors in Seizure Development When Breathing Hyperbaric OxygenРоль ГАМК-рецепторов в развитии судорог, индуцированных гипербарическим кислородомAlekseevaO. S.АлексееваО. С.
Russian Federation
osa72@inbox.ruPlatonovaT. F.ПлатоноваТ. Ф.
Russian Federation
osa72@inbox.ruDemchenkoI. T.ДемченкоИ. Т.
Russian Federation
osa72@inbox.ruSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of SciencesИнститут эволюционной физиологии и биохимии им. И.М. Сеченова Российской академии наук1506202511169449561307202513072025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-8139/article/view/687414

The use of hyperbaric oxygen (HBO2) in medicine and in underwater diving is associated with the risk of its toxic (convulsant) effect on the central nervous system, the pathophysiological mechanisms of which have not been sufficiently studied. A common hypothesis about the mechanism of HBO2-induced convulsions is the idea that extreme hyperoxia suppresses GABAergic function with subsequent increase in CNS excitation, leading to convulsions. The deficit of GABAergic function in HBO2 is due to a decrease in the synthesis of the mediator, while the involvement of other components of inhibitory neurotransmission, in particular, GABA receptors, remains unclear. The aim of this work was to study the involvement of GABA receptors in the development of hyperbaric oxygen convulsions. In the course of the work, motor convulsions in HBO2 were assessed in rats that were injected with GABA receptor agonists: muscimol or baclofen into the lateral ventricle of the brain before hyperoxic exposure. The affinity of GABA receptors to these drugs was also assessed against the background of an increased level of cerebral GABA caused by intraventricular administration of nipecotic acid. New data from the studies are: (a) activation of GABA-A receptors with muscimol delayed the onset of seizures in HBO2, (b) the GABA-B receptor agonist baclofen weakened the development of hyperbaric oxygen seizures, but its anticonvulsant effect was reliably lower than that of muscimol, (c) the anticonvulsant efficacy of muscimol and baclofen was preserved with an increase in extracellular GABA caused by inhibition of GABA transporters with nipecotic acid. The affinity of GABA-A and GABA-B receptors to the inhibitory neurotransmitter did not change under conditions of hyperbaric hyperoxia.

Использование гипербарического кислорода (ГБО2) в медицине и при подводных погружениях сопряжено с риском его токсического (судорожного) действия на ЦНС, патофизиологические механизмы которого изучены недостаточно. Распространенной гипотезой о механизме ГБО2-вызываемых судорог является представление о том, что экстремальная гипероксия подавляет ГАМК-ергическую функцию с последующим усилением возбуждения ЦНС, приводящего к судорогам. Дефицит ГАМК-ергической функции в ГБО2 обусловлен снижением синтеза медиатора, тогда как вовлечение других компонентов тормозной нейротрансмиссии, в частности рецепторов ГАМК, остается неясным. Целью настоящей работы являлось изучение причастности ГАМК-рецепторов к развитию гипербарических кислородных судорог. При выполнении работы оценивались моторные судороги в ГБО2 у крыс, которым перед гипероксической экспозицией в боковой желудочек головного мозга вводили агонисты ГАМК-рецепторов: мусцимол или баклофен. Аффинность рецепторов ГАМК к этим препаратам оценивалась также на фоне повышенного уровня мозговой ГАМК, вызываемого внутрижелудочковым введением нипекотовой кислоты. Новыми данными выполненных исследований являются: 1) активация ГАМК-А-рецепторов с помощью мусцимола задерживала появление судорог в ГБО2; 2) агонист ГАМК-В-рецепторов – баклофен, ослаблял развитие гипербарических кислородных судорог, но его противосудорожный эффект был достоверно ниже, чем у мусцимола; 3) противосудорожная эффективность мусцимола и баклофена сохранялась при повышении внеклеточного ГАМК, вызываемого ингибированием ГАМК-транспортеров с помощью нипекотовой кислоты. Аффинность ГАМК-А- и ГАМК-В-рецепторов к тормозному нейромедиатору не изменялась в условиях гипербарической гипероксии.

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