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Effect of Valproate, Lamotrigine and Levetiracetam on Excitability and Firing Properties of CA1 Neurons in Rat Brain Slices

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Abstract

The purpose of this study was to analyze the rapid effects of the antiepileptic drugs valproate, lamotrigine, and levetiracetam on excitability and firing properties of hippocampal neurons. The drug effects on resting potential, action potential, and repetitive firing properties were studied in whole-cell current-clamp recordings of CA1 neurons in rat brain slices. Lamotrigine changed action potential rising slope by −24 ± 38 V/s (mean ± SD), peak amplitude by −6.8 ± 5.0 mV, and maximum firing frequency by −60 ± 13%. Lamotrigine thereto increased the voltage threshold by 4.3 ± 4.2 mV and augmented the action potential attenuation during repetitive firing. All effects were significant (P < 0.01 to P < 0.0002) compared to control cells. Valproate and levetiracetam showed no significant effects on these parameters. None of the tested drugs had a significant effect on the resting potential. The lamotrigine effects are consistent with sodium channel blocking which may explain or contribute to the antiepileptic mode of action. Valproate and levetiracetam did not show these effects and the mechanism of their antiepileptic action need to be different. These findings (valproate) differ in some respects from findings reported in cultured or dissociated neurons. In a slice where the neurons have largely preserved connections, drug effects are likely to be more similar to the therapeutic action in the brain.

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Acknowledgments

The support from Karolinska Institutets Fonder, GlaxoSmithKline (Research Grant in Epilepsy) and Pfizer (Research Grant in Neuroscience) is gratefully acknowledged. The authors wish to thank Orion Pharma, Espoo, Finland (valproate) and UCB Pharma, Braine-L’Alleude, Belgium (levetiracetam) for their kind gift of drugs.

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Authors and Affiliations

  1. Department of Clinical Neuroscience, Section of Clinical Neurophysiology, Karolinska Institutet, 171 76, Stockholm, Sweden

    Marita Englund, Lars Hyllienmark & Tom Brismar

  2. Department of Clinical Neuroscience, Section of Neurology, Karolinska Institutet, 171 76, Stockholm, Sweden

    Lars Hyllienmark

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  1. Marita Englund
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  2. Lars Hyllienmark
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  3. Tom Brismar
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Correspondence to Lars Hyllienmark.

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Englund, M., Hyllienmark, L. & Brismar, T. Effect of Valproate, Lamotrigine and Levetiracetam on Excitability and Firing Properties of CA1 Neurons in Rat Brain Slices. Cell Mol Neurobiol 31, 645–652 (2011). https://doi.org/10.1007/s10571-011-9660-y

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  • DOI: https://doi.org/10.1007/s10571-011-9660-y

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