Normobaric intermittent postconditioning corrects development of anxiety-depressive state in the experimental model of post-traumatic stress disorder

Abstract

BACKGROUND: Despite the rapid increase in the prevalence of post-traumatic stress disorder, there are still no effective drugs for its treatment, therefore, the development of non-drug approaches is an extremely urgent task, which this study is aimed at solving.

AIM: To estimate experimentally the therapeutic effects of hypoxic postconditioning using intermittent normobaric hypoxia in a model of post-traumatic stress disorder-like pathology in rats.

MATERIALS AND METHODS: In the rat model of post-traumatic stress disorder “stress–restress”, the effects of three postconditioning regimes were investigated: three 5-min episodes of hypoxia with 9% oxygen interspaced with 15-min intervals of normoxia (reoxygenation) per day for 3 days after pathogenic stress (hypoxia/normoxia mode); three 5-min episodes of 9% hypoxia interspaced with 3-min intervals of hyperoxia with 30% oxygen in the mixture, per day for 3 days (hypoxia/hyperoxia mode); five 5-min episodes of 12% hypoxia and 3-min 30% O₂ hyperoxia per day for 9 days (hypoxia/hyperoxia mode, prolonged). Animal behavior, hypothalamic-pituitary-adrenal axis function and indices of general blood analysis were analysed.

RESULTS: All the modes of normobaric postconditioning to a greater or lesser extent had a corrective effect on the manifestation of pathological symptomatology; however, triple hypoxia/hyperoxia postconditioning was more effective than other modes in terms of the totality of protective and absence of side effects.

CONCLUSIONS: The results suggest that postconditioning using intermittent normobaric hypoxia/hyperoxia for the treatment of anxiety-depressive disorders in humans, including post-traumatic stress disorder, may be a promising approach.

Keywords

anxiety-depressive disorders / experimental post-traumatic stress disorder / anxiety / normobaric hypoxia / hypoxia/hyperoxia / anxiolytic effect

References

[1] Deev IA, Kobyakova OS, Starodubov VI, et al. Morbidity of the entire population of Russia in 2023 with a diagnosis established for the first time in life: statistical materials . Moscow; 2024. 152 p. doi: 10.21045/978-5-94116-159-1-2024

[2] Деев И.А., Кобякова О.С., Стародубов В.И., и др. Заболеваемость всего населения России в 2023 году с диагнозом, установленным впервые в жизни: статистические материалы. Москва: ЦНИИОИЗ, 2024. 152 с. doi: 10.21045/978-5-94116-159-1-2024

[3] Vasilieva AV, Karavaeva TA, Radionov DS. Pharmacotherapy algorithm for post-traumatic stress disorder. V.M. Bekhterev Review of Psychiatry and Medical Psychology. 2023;57(3):80–91. EDN: VMKTRD doi: 10.31363/2313-7053-2023-762

[4] Васильева А.В., Караваева Т.А., Радионов Д.С. Алгоритм лекарственной терапии посттравматического стрессового расстройства // Обозрение психиатрии и медицинской психологии имени В.М. Бехтерева. 2023. Т. 57, № 3. С. 80–91. EDN: VMKTRD doi: 10.31363/2313-7053-2023-762

[5] Rybnikova EA, Mironova VI, Tyulkova EI, et al. Anxiolytic effect of moderate hypobaric hypoxia in rats in the model of posttraumatic stress disorder. I.P. Pavlov Journal of Higher Nervous Activity . 2008;58(4):486–492. EDN: JJRMCF

[6] Рыбникова Е.А., Миронова В.И., Тюлькова Е.И., и др. Анксиолитический эффект умеренной гипобарической гипоксии у крыс в модели посттравматического стрессового расстройства // Журнал высшей нервной деятельности им. И.П. Павлова. 2008. Т. 58, № 4. С. 486–492. EDN: JJRMCF

[7] Karash YM, Strelkov RB, Chizhov AYa. Normobaric hypoxia in treatment, prevention and rehabilitation. Moscow: Meditsina; 1988. 352 р. (In Russ.)

[8] Караш Ю.М., Стрелков Р.Б., Чижов А.Я. Нормобарическая гипоксия в лечении, профилактике и реабилитации. Москва: Медицина, 1988. 352 c.

[9] Kolchinskaya AZ, Tsyganova TN, Ostapenko LA. Normobaric interval hypoxic training in medicine and sport . Moscow: Meditsina; 2003. 408 р. (In Russ.) EDN: QLEFFN

[10] Колчинская А.З., Цыганова Т.Н., Остапенко Л.А. Нормобарическая интервальная гипоксическая тренировка в медицине и спорте. Москва: Медицина, 2003. 408 c. EDN: QLEFFN

[11] Serebrovskaya TV, Nikolsky IS, Ishchuk VA, et al. Human adaptation to periodic hypoxia: effect on haematopoietic stem cells and immune system. Bulletin of the International Academy of Sciences. Russian Section. 2010;(2):12–17. EDN: NDTXAB

[12] Серебровская Т.В., Никольский И.С., Ищук В.А., и др. Адаптация человека к периодической гипоксии: влияние на гемопоэтические стволовые клетки и иммунную систему // Вестник Международной академии наук. Русская секция. 2010. № 2. С. 12–17. EDN: NDTXAB

[13] Behrendt T, Bielitzki R, Behrens M, et al. Effects of intermittent hypoxia–hyperoxia on performance- and health-related outcomes in humans: A systematic review. Sports Med Open . 2022;8(1):70. doi: 10.1186/s40798-022-00450-x

[14] Behrendt T., Bielitzki R., Behrens M., et al. Effects of intermittent hypoxia–hyperoxia on performance- and health-related outcomes in humans: A systematic review // Sports Med Open. 2022. Vol. 8, N 1. P. 70. doi: 10.1186/s40798-022-00450-x

[15] Uzun AB, Iliescu MG, Stanciu LE, et al. Effectiveness of intermittent hypoxia–hyperoxia therapy in different pathologies with possible metabolic implications. Metabolites. 2023;13(2):181. doi: 10.3390/metabo13020181

[16] Uzun A.B., Iliescu M.G., Stanciu L.E., et al. Effectiveness of intermittent hypoxia–hyperoxia therapy in different pathologies with possible metabolic implications // Metabolites. 2023. Vol. 13, N 2. Р. 181. doi: 10.3390/metabo13020181

[17] Zenko MY, Rybnikova EA. Hypoxic adaptation and training: historical, biomedical and sports aspects. Aerospace and Environmental Medicine . 2021;55(1):20–26. EDN: NCNYWM doi: 10.21687/0233-528X-2021-55-1-20-26

[18] Зенько М.Ю., Рыбникова Е.А. Гипоксическая адаптация и тренировка: исторические, биомедицинские и спортивные аспекты // Авиакосмическая и экологическая медицина. 2021. Т. 55, № 1. С. 20–26. EDN: NCNYWM doi: 10.21687/0233-528X-2021-55-1-20-26

[19] Liberzon I, Krstov M, Young EA. Stress-restress: effects on ACTH and fast feedback. Psychoneuroendocrinology . 1997;22(6):443–453 . doi: 10.1016/S0306-4530(97)00044-9

[20] Liberzon I., Krstov M., Young E.A. Stress-restress: effects on ACTH and fast feedback // Psychoneuroendocrinology. 1997. Vol. 22, N 6. Р. 443–453. doi: 10.1016/S0306-4530(97)00044-9

[21] Zenko MY, Baranova KA, Kukina MV, Rybnikova E.A. The effects of various modes of interval hypoxic training in experimental models of anxiety and depression in rats. I.P. Pavlov Journal of Higher Nervous Activity . 2023;73(6):845–856. EDN: XLISSQ doi: 10.31857/S004446772306014X

[22] Зенько М.Ю., Баранова К.А., Кукина М.В., Рыбникова Е.А. Эффекты различных режимов интервальных гипоксических тренировок в экспериментальных моделях тревожно-депрессивных состояний на грызунах // Журнал высшей нервной деятельности им. И.П. Павлова. 2023. Т. 73, № 6. С. 845–856. EDN: XLISSQ DOI: 10.31857/S004446772306014X

[23] Hall CS. Emotional behavior in the rat. III. The relationship between emotionality and ambulatory activity. J Comp Psychol. 1936;22(3):345. doi: 10.1037/h0059253

[24] Hall C.S. Emotional behavior in the rat. III. The relationship between emotionality and ambulatory activity // J Comp Psychol. 1936. Vol. 22, N 3. Р. 345. doi: 10.1037/h0059253

[25] Pellow S, Chopin P, File SE, et al. Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods. 1985;14(3):149–167. doi: 10.1016/0165-0270(85)90031-7

[26] Pellow S., Chopin P., File S.E., et al. Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat // J Neurosci Methods. 1985. Vol. 14, N 3. Р. 149–167. doi: 10.1016/0165-0270(85)90031-7

[27] Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2007;2(2):322–328. doi: 10.1038/nprot.2007.44

[28] Walf A.A., Frye C.A. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents // Nat Protoc. 2007. Vol. 2, N 2. Р. 322–328. doi: 10.1038/nprot.2007.44

[29] Yehuda R. Neuroendocrine aspects of PTSD. In: Holsboer F, Ströhle A, eds. Anxiety and Anxiolytic Drugs. Handbook of Experimental Pharmacology . Springer, Berlin: Heidelberg; 2005. Vol. 169. P. 371–403. doi: 10.1007/3-540-28082-0_13

[30] Yehuda R. Neuroendocrine aspects of PTSD. In: Holsboer F., Ströhle A., eds. Anxiety and Anxiolytic Drugs. Handbook of Experimental Pharmacology. Springer, Berlin, Heidelberg, 2005. Vol. 169. Р. 371–403. doi: 10.1007/3-540-28082-0_13

[31] Baranova KA, Zenko MY, Rybnikova EA. Influence of interval hypoxic training in different regimes on the blood parameters of rats. J Evol Biochem Phys. 2024;60:306–315. doi: 10.1134/S0022093024010228

[32] Baranova K.A., Zenko M.Y., Rybnikova E.A. Influence of interval hypoxic training in different regimes on the blood parameters of rats // J Evol Biochem Phys. 2024. Vol. 60. P. 306–315. doi: 10.1134/S0022093024010228

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