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A pentylenetetrazole-induced generalized seizure in early life enhances the efficacy of muscarinic receptor coupling to G-protein in hippocampus and neocortex of adult rat

Authors

  • Soizic Potier,

    1. Ste-Justine Hospital Research Centre & Department of Pediatrics, Montreal, Québec, Canada
    2. Department of Physiology, Montreal, Faculty of Medicine, Université de Montréal, Québec, Canada
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  • Jacques Sénécal,

    1. Department of Physiology, Montreal, Faculty of Medicine, Université de Montréal, Québec, Canada
    2. Department of Pathology and Cellular Biology, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada
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  • Jean-Guy Chabot,

    1. Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Québec, Canada
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  • Caterina Psarropoulou,

    1. Ste-Justine Hospital Research Centre & Department of Pediatrics, Montreal, Québec, Canada
    2. Department of Physiology, Montreal, Faculty of Medicine, Université de Montréal, Québec, Canada
    3. Centre de recherche en sciences neurologiques, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada
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    • *

      Present address: Department of Biological Applications and Technologies, University of Ioannina, Ioannina 45110, Greece.

  • Laurent Descarries

    1. Department of Physiology, Montreal, Faculty of Medicine, Université de Montréal, Québec, Canada
    2. Department of Pathology and Cellular Biology, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada
    3. Centre de recherche en sciences neurologiques, Faculty of Medicine, Université de Montréal, Montreal, Québec, Canada
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Dr L. Descarries, as above.3
E-mail: laurent.descarries@UMontreal.CA

Abstract

We have previously shown that exposure to the anti-cholinesterase eserine provokes interictal-like discharges in the CA3 area of hippocampal slices from adult rats in which a generalized seizure has been induced by pentylenetetrazole (PTZ) when immature (at 20 days). Such increased responsiveness to acetylcholine (ACh) was not associated with any change in hippocampal acetylcholine or γ-aminobutyric acid (GABA) content, GABAergic inhibition or density of ACh innervation, but was blocked by the muscarinic receptor antagonist atropine. We therefore turned to quantitative radioligand binding autoradiography, in situ hybridization and the [35S]GTPγS method to assess the properties of hippocampal and neocortical muscarinic receptors in adult rats having experienced a PTZ seizure at P20. The densities of M1 and M2 receptor binding sites, respectively labeled with [3H]pirenzepine and [3H]AFDX-384, as well as the amount of m1, m2 and m3 receptor mRNAs, did not differ from control in the hippocampus and neocortex of these rats. In contrast, in PTZ rats, both brain regions displayed a marked increase in [35S]GTPγS incorporation stimulated by ACh, bethanechol and particularly oxotremorine. This finding indicates that a generalized seizure in immature rat can entail a long-term and presumably permanent increase in the efficacy of G-protein coupling to muscarinic receptors in the hippocampus and neocortex of the adult. By analogy, such a mechanism could account for the susceptibility to epilepsy of human adults having suffered from prolonged convulsions in early life.

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