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Three neurosteroids as well as GABAergic drugs do not convert immediate postictal potentiation to depression in immature rats

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Abstract

Background

Postictal potentiation presented immediately after cortical seizures in immature rats might be due to imbalance between excitation and inhibition. The aim of the present study was to determine whether augmentation of inhibition mediated by GABAA receptors could also suppress the postictal potentiation.

Methods

Twelve-day old rats with implanted electrodes were used in our study. Five drugs were tested: the agonist muscimol, the positive modulator midazolam and three neurosteroids affecting GABAA receptors—allopregnanolone, pregnanolone sulphate and pregnanolone glutamate.

Results

None of the five drugs was able to suppress potentiation appearing immediately after cortical epileptic afterdischarges, but all of them exhibited delayed anticonvulsant action 10 (in the case of midazolam and muscimol) or 20 min (all three steroids) after cortical seizures.

Conclusion

Our results support a role of GABA in augmentation of cortical after discharges after longer intervals, whereas immediate postictal potentiation is not affected by GABAergic drugs. Due to similar effect with GABAergic drugs, the main mechanism of action of the three steroids tested is potentiation of GABAergic inhibition.

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Acknowledgements

This study was funded by a project PHARMABRAIN, reg.no CZ_02.1.01/0.0/0.0/16_025/0007444 (co-supported by EU), by a grant of the Czech Grant Agency 18-09296S and a research Project No.67985823 of the Czech Academy of Sciences. The authors would like to express their thanks to Ms.Irinka Nesev for excellent technical assistance.

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Authors and Affiliations

  1. Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

    Pavel Mareš, Karel Valeš & Hana Kubová

  2. Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic

    Eva Kudová

  3. National Institute of Mental Health, Klecany, Czech Republic

    Karel Valeš

  4. Department of Developmental Epileptology, Institute of Physiology, Czech Academy of Sciences, Vídenská 1083, 14220, Prague, Czech Republic

    Pavel Mareš

Authors
  1. Pavel Mareš
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  2. Eva Kudová
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  3. Karel Valeš
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  4. Hana Kubová
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Contributions

PM planned and performed experiments, evaluated the data and prepared the manuscript. EK synthesized the neurosteroids and participated in planning of experiments. KV participated in planning the experiments and in preparation of manuscript. HK participated in planning and evaluation of the experiments and in preparation of manuscript.

Corresponding author

Correspondence to Pavel Mareš.

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The authors declare no conflict of interest.

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Mareš, P., Kudová, E., Valeš, K. et al. Three neurosteroids as well as GABAergic drugs do not convert immediate postictal potentiation to depression in immature rats. Pharmacol. Rep 72, 1573–1578 (2020). https://doi.org/10.1007/s43440-020-00113-2

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  • DOI: https://doi.org/10.1007/s43440-020-00113-2

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