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

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Abstract

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).

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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

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2. 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.

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3. 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.

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


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