Effect of early and late pharmacological correction with GABA derivatives on cognitive disorders in offspring of rats with experimental preeclampsia

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access


BACKGROUND: Preeclampsia is a serious complication of pregnancy which augments the risk of cognitive disorders in the offspring at different stages of life. Presently, there are no methods with proven effectiveness for correction of post-hypoxic disorders in children of mothers with preeclampsia.

AIM: To assess the cognitive functions of the offspring of rats with experimental preeclampsia (EP) through early (40th to 70th day of life) and late (24th to 25th month of life) pharmacological correction with gamma aminobutyric acid (GABA) derivatives: Succicard, Salifen, Phenibut, and the drug of comparison–Pantogam.

MATERIALS AND METHODS: EP was modeled by replacing drinking water with 1.8% sodium chloride solution in rats from the first day of pregnancy to delivery. In the offspring, short-term and long-term memory was studied at the age of 3–4, 18–19, and 25–26 months in the Novel object recognition test and Barnes Maze test. The functioning of the GABAergic and dopaminergic systems (which play an essential role in the development of memory) was evaluated by cases of convulsions after administering corazol at a dose of 20 mg/kg intraperitoneally (model of corazol kindling) and by haloperidol-induced catalepsy (haloperidol at a dose of 0.3 mg/kg intraperitoneally), respectively.

RESULTS: Early and late pharmacological correction with GABA derivatives–succicard, Salifen, Phenibut, and comparison drug, Pantogam–neutralized the negative effect of EP on the function of GABAergic and dopaminergic systems in the offspring of the experimental groups. Therapy with Succicard in puberty and long-term periods of life contributed to the improvement of short-term and long-term memory in the offspring of rats with EP. Thus, it could be reasonable enough to develop a drug against cognitive disorders in children of mothers with preeclampsia.

CONCLUSION: In the offspring of rats with EP, short-term and long-term disorders of memory in the functioning of the GABAergic and dopaminergic systems were noted in the early and late stages of the individual development. Pharmacological correction with GABA derivatives improves cognitive processes and the functioning of neurotransmitter systems in the offspring of rats with complicated pregnancy. The highest effectiveness was demonstrated by succicard, and was comparable with or superior to the Pantogam (standard drug).

Full Text

Restricted Access

About the authors

Elena A. Muzyko

Volgograd State Medical University

Email: muzyko.elena@mail.ru
ORCID iD: 0000-0003-0535-9787
SPIN-code: 9939-9414
ResearcherId: AAD-9996-2019

Post-graduate student of the Department of Pharmacology and Pharmacy

Russian Federation, 400131, Volgograd, Pavshih Bortcov sq., 1

Valentina N. Perfilova

Volgograd State Medical University

Email: vnperfilova@mail.ru
ORCID iD: 0000-0002-2457-8486
SPIN-code: 3291-9904
ResearcherId: P-7142-2015

doctor of science (Biology), professor, professor of the department of pharmacology and pharmacy

Russian Federation, 400131, Volgograd, Pavshih Bortcov sq., 1

Ivan N. Tyurenkov

Volgograd State Medical University

Email: fibfuv@mail.ru
ORCID iD: 0000-0001-7574-3923
SPIN-code: 6195-6378
ResearcherId: P-7173-2015

Doctor of Medical Sciences, Corresponding Member of the Russian Academy of Sciences, Professor, Head of the Department of Pharmacology and Pharmacy

Russian Federation, 400131, Volgograd, Pavshih Bortcov sq., 1

Olga S. Vasil'eva

Herzen State Pedagogical University Russian Federation

Author for correspondence.
Email: kohrgpu@yandex.ru
ORCID iD: 0000-0002-7779-8861
SPIN-code: 9820-9881
ResearcherId: U-6205-2019

candidate of science (Chemistry), senior researcher of Problem Laboratory of Nitro Compounds, Department of Organic Chemistry

Russian Federation, 191186, St. Petersburg, Moika Embankment, 48


  1. Kay VR, Rätsep MT, Figueiró-Filho EA, et al. Preeclampsia may influence offspring neuroanatomy and cognitive function: a role for placental growth factor. Biology of Reproduction. 2019;101(2):271–83. doi: 10.1093/biolre/ioz095
  2. Tuovinen S, Räikkönen K, Kajantie E, et al. Hypertensive disorders in pregnancy and cognitive decline in the offspring up to old age. Neurology. 2012;79(15):1578–82. doi: 10.1212/WNL.0b013e31826e2606
  3. Morsing E, Maršál K. Pre-eclampsia – an additional risk factor for cognitive impairment at school age after intrauterine growth restriction and very preterm birth. Early Human Development. 2014;90(2):99–101. doi: 10.1016/j.earlhumdev.2013.12.002
  4. Wade M, Jenkins JM. Pregnancy hypertension and the risk for neuropsychological difficulties across early development: A brief report. Child Neuropsychology. 2016;22(2):247–54. doi: 10.1080/ 09297049.2014.958070
  5. Nalivaeva NN, Turner AJ, Zhuravin IA. Role of prenatal hypoxia in brain development, cognitive functions, and neurodegeneration. Frontiers in Neuroscience. 2018;12:825. doi: 10.3389/fnins.2018.00825
  6. Muzyko EA, Tkacheva GA, Perfilova VN, et al. Cognitive Dysfunction in the Offspring from Rats with Experimental Preeclampsia at the Early and Late Stages of Ontogenesis and Its Correction by GABA Derivatives. Russian Journal of Physiology. 2020;106(6):765–82. (In Russ). doi: 10.31857/S0869813920060084
  7. Li J, Chen L, Guo F, et al. The Effects of GABAergic System under Cerebral Ischemia: Spotlight on Cognitive Function. Neural Plasticity. 2020;2020:8856722. doi: 10.1155/2020/8856722
  8. Cropley VL, Fujita M, Innis RB, et al. Molecular imaging of the dopaminergic system and its association with human cognitive function. Biological Psychiatry. 2006;59(10):898–907. doi: 10.1016/j.biopsych.2006.03.004
  9. Burchynskyi SH. GABA-ergic agents in the pharmacotherapy of chronic cerebral ischemia. International Neurological Journal. 2015;(1):101–5. (In Russ).
  10. Ordyan NE, Akulova VK, Pivina SG, et al. Perinatal Hypoxia-Induced Impairments of Behavioral and Hormonal Stress Responses in Rats and Their Correction by a novel GABA Derivative. Journal of Evolutionary Biochemistry and Physiology. 2019;55(1):59–64. (In Russ). doi: 10.1134/S0044452919010091
  11. Tyurenkov IN, Perfilova VN, Mikhailova LI, et al. Comparative Study of the Effects of New Neuroactive Amino Acid Derivatives on the Postnatal Development of the Rat's Offspring with Experimental Preeclampsia. Annals of the Russian Academy of Medical Sciences. 2014;69(9–10):123–30. (In Russ). doi: 10.15690/vramn.v69i9-10.1141
  12. Sunyer B, Patil S, Höger H, et al. Barnes maze, a useful task to assess spatial reference memory in the mice. Protocol Exchange. 2007;10:1–18. doi: 10.1038/nprot.2007.390
  13. Manveljan EA, Baturin VA, Bulgakova MD, et al. Circadian variations in the intensity of haloperidol’s catalepsy in female rats without and after estrogen used. Biomedicine. 2012;(2):14–21. (In Russ).
  14. Daniel JM, Sulzer JK, Hulst JL. Estrogen increases the sensivity of ovariectomized rats to the disruptive effects produced by antagonism of D2 but not D1 dopamine receptors during performance of a response leaning task. Hormones and Behavior. 2006;49(1):38–44. doi: 10.1016/j.yhbeh.2005.05.001
  15. McHenry J, Carrier N, Hull E, et al. Sex differences in anxiety and depression: role of testosterone. Frontiers in Neuroendocrinology. 2014;35(1):42–57. doi: 10.1016/j.yfrne.2013.09.001
  16. Gumusoglu SB, Chilukuri AS, Santillan DA, et al. Neurodevelopmental outcomes of prenatal preeclampsia exposure. Trends in Neurosciences. 2020;43(4):253–68. doi: 10.1016/j.tins.2020.02.003
  17. Cunha-Rodrigues MC, do Nascimento Balduci CT, Tenório F, Barradas PC. GABA function may be related to the impairment of learning and memory caused by systemic prenatal hypoxia-ischemia. Neurobiology of Learning and Memory. 2018;149:20–7. doi: 10.1016/j.nlm.2018.01.004
  18. Giannopoulou I, Pagida MA, Briana DD, et al. Perinatal hypoxia as a risk factor for psychopathology later in life: the role of dopamine and neurotrophins. Hormones. 2018;17(1):25–32. doi: 10.1007/s42000-018-0007-7
  19. Otellin VA, Khozhai LI, Tyurenkov IN. The effect of phenibut on the number of gabaergic neurons in rat neocortex during juvenile and prepuberant periods after acute hypoxia in the perinatal period. Eksperimental’naya i Klinicheskaya Farmakologiya. 2020;83(2):3–7. (In Russ). doi: 10.30906/0869-2092-2020-83-2-3-7
  20. Mitrokhin KV, Baranishin AA, Mitrohin KV, Baranishin AA. Classification and brief description of drug analogues, derivatives of gamma-aminobutyric acid and toxic substances influencing GABA-ergic connections. Russian Journal of Anaesthesiology and Reanimatology. 2018;(6):22–30 (In Russ.). doi: 10.17116/anaesthesiology201806122.

Supplementary files

Supplementary Files
1. Fig. 1. Effects of early and late pharmacological treatments with GABA derivatives on short-term working memory (s, M ± m) of offspring (aged 3, 18, and 25 months) of rats with Experimental Preeclampsia using the Novel Object Recognition test.

Download (169KB)
2. Fig. 2. Effects of GABA derivatives on duration (s, М ± m) of verticalization induced by administration of haloperidol in offspring of rats with Experimental Preeclampsia at the age of 4, 19, and 26 months.

Download (249KB)

Copyright (c) 2021 Muzyko E.A., Perfilova V.N., Tyurenkov I.N., Vasil'eva O.S.

Свидетельство о регистрации СМИ ПИ № ФС77-76803 от 24 сентября 2019 года выдано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies