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Sodium- and magnesium-valproate in vivo modulate glutamatergic and GABAergic synapses in the medial prefrontal cortex

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Abstract

Rationale

Valproic acid (VPA) is a psychoactive drug currently used for the treatment of epilepsy. Recently it has been introduced in psychiatry for the treatment of bipolar disorders, aggression, impulsivity, and resistant schizophrenia, although the mechanism by which VPA acts on these psychiatric diseases remains still unknown.

Objectives

The aim of this study was to analyze the distinct effects of sodium-(Na-) and magnesium-valproate (Mg-VPA) in pyramidal neurons of the medial prefrontal cortex (mPFC) and their interactions with gamma-aminobutyric acid (GABA) and excitatory amino acid responses.

Materials and methods

In vivo electrophysiology and microiontophoresis techniques were used to attend these goals.

Results

Both VPA salts decreased spontaneous neuronal firing activity in greater than 60% of recorded pyramidal neurons as well as potentiated GABA inhibitions. When injected at equal concentrations and currents, Mg-VPA blocked the excitatory responses induced by N-methyl-d-aspartate (NMDA) more frequently than Na-VPA. Both VPA salts equally blocked the excitatory responses of quisqualate and kainate.

Conclusions

These data suggest that VPA salts significantly modulate the activity of excitatory amino acid at mPFC pyramidal neurons and this mechanism should explain the therapeutic effects of valproate in psychiatric diseases involving NMDA, AMPA, and kainate receptors at the mPFC level.

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Acknowledgements

The authors wish to thank Sigma-Tau, Pomezia (Italy), which kindly supplied sodium- and magnesium-valproate and the drugs used in this work. G.G. received a salary award and a grant from Fonds de la Recherche en Santé du Quebéc (no.1991) and from Canadian Psychiatric Research Foundation (CPRF). LJ received a research grant (no. 7010861) from the Italian Ministry of University and Scientific–Technological Research (MURST). The authors also wish to thank Dr. Paolo Montuschi (Institute of Pharmacology, Catholic University, Rome), Dr. Umberto Lombardi for their helpful assistance, Mr. Noam Katz for editing the manuscript, and Dr. Guy Debonnel and Dr. Guillaume Lucas (McGill University, Montreal) for feedback on the manuscript and for stimulating discussion.

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Authors and Affiliations

  1. Department of Psychiatry, McGill University, Montreal, Quebec, Canada

    Gabriella Gobbi

  2. Centre de Recherche Fernand-Seguin, Université de Montréal, Montreal, Quebec, Canada

    Gabriella Gobbi

  3. Institute of Psychiatry, Faculty of Medicine, Catholic University of S. Heart, Rome, Italy

    Luigi Janiri

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  1. Gabriella Gobbi
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Correspondence to Gabriella Gobbi.

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Gobbi, G., Janiri, L. Sodium- and magnesium-valproate in vivo modulate glutamatergic and GABAergic synapses in the medial prefrontal cortex. Psychopharmacology 185, 255–262 (2006). https://doi.org/10.1007/s00213-006-0317-3

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  • DOI: https://doi.org/10.1007/s00213-006-0317-3

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