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Electrophysiological and behavioral properties of 4-aminopyridine-induced epileptic activity in mice

Abstract

4-aminopyridine (4-AP) is a widely used drug that induces seizure activity in rodents, especially in rats, although there is no consensus in the literature on the dose to be used in mice. The aim of the present study was to investigate the effect of the intraperitoneal administration of 4-AP in two doses (4 and 10 mg/kg) in vivo. EEG, movement, and video recordings were made simultaneously in male B6 mice to specify the details of the seizures and to determine whether there is a suitable non-lethal dose for seizure induction and for further molecular studies. Seizure behavior in mice differs from that seen in rats, with no characteristic stages of epileptic seizures, but with spiking and seizure activity. Seizure activity, although produced at both doses without being lethal, induced different changes of the EEG pattern. Smaller dose induced a lower amplitude seizure activity, decreased spiking activity and later onset of seizures, while higher dose induced a much more intense brain seizure activity and severe trembling. It is concluded that the intraperitoneal administration of 4-AP at a dose of 10 mg/kg induces explicit seizure activity in mice which is repeatable and can be suitable for further molecular research.

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Data availability

The raw generated data are available from the corresponding author (FZF) on request accessibility.

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Acknowledgements

The supportive work of the colleagues at ELTE Research Group of Proteomics and Institute of Experimental Medicine is highly appreciated.

Funding

This work was supported by the National Research, Development, and Innovation Office of Hungary Grants (2017-1.2.1-NKP-2017-00002 to F.Z.F., and Z.F.) the National Research, Development and Innovation Office (grants: NKFIH K 120143, K 113147) and FIEK_16-1-2016-0005 Grant to L.R., Zs. B. and G. J. The Bolyai János Scholarship of the Hungarian Academy of Sciences and Scholarship of the New National Excellence Foundation (UNKP-19-4-PPKE-9) granted for Z.F. is also acknowledged.

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Correspondence to F. Z. Fedor.

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The authors declare that they have no conflict of interest.

Ethical statement

In all cases, our experiments were conducted in compliance with EU directive in force (2010/63/EU) and in accordance with the applicable government decree (40/2013. (II. 14.)), making sure that the animals suffer as little as possible.

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Fedor, F.Z., Paraczky, C., Ravasz, L. et al. Electrophysiological and behavioral properties of 4-aminopyridine-induced epileptic activity in mice. BIOLOGIA FUTURA 71, 427–434 (2020). https://doi.org/10.1007/s42977-020-00047-z

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Keywords

  • 4-Aminopyridine (4-AP)
  • Epilepsy model
  • EEG
  • B6 mice
  • In vivo studies
  • Behavior