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Alterations in Nitric Oxide-Stimulated Endogenous ADP-Ribosylation Associated with Long-Term Potentiation in Rat Hippocampus

Authors

  • Ronald S. Duman,

    Corresponding author
    1. Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
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  • Rose Z. Terwilliger,

    1. Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
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  • Eric J. Nestler

    1. Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
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Address correspondence and reprint requests to Dr. R. S. Duman at Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, U.S.A.

Abstract

Abstract: The present study examines the possible involvement of nitric oxide (NO)-stimulated endogenous ADP-ribosylation in long-term potentiation (LTP). LTP was induced in hippocampal slices by stimulation of Schaffer collateral inputs to the CA1 pyramidal neurons. Basal and sodium nitroprusside (SNP), which generates NO, stimulation of endogenous ADP-ribosylation was then studied in CA1 subfields isolated from the slices. Control slices received no treatment or were tetanized in the presence of aminophosphonovaleric acid, an NMDA receptor antagonist that blocks the development of LTP. SNP-stimulated ADP-ribosylation of endogenous proteins was reduced by 40–70% in LTP slices relative to control slices. LTP was also associated with a small but significant reduction in basal ADP-ribosylation activity. The results demonstrate that the induction of LTP is associated with regulation of endogenous ADP-ribosylation and suggest a role for this type of covalent modification in some aspect of LTP.

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