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Decrease in the Reactivity of Locus Coeruleus Neurons to Hypotension after an Increase in their Tyrosine Hydroxylase Content: A Subregional In Vivo Voltammetry Study in the Rat

Authors

  • Cédric Vachette,

    Corresponding author
    1. Université Claude Bernard et CNRS UMR 105, Laboratoire de Neuropharmacologie, Faculté de Pharmacie, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France
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  • Odile Bourde,

    1. Université Claude Bernard et CNRS UMR 105, Laboratoire de Neuropharmacologie, Faculté de Pharmacie, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France
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  • Jean-Yves Gillon,

    1. Université Claude Bernard et CNRS UMR 105, Laboratoire de Neuropharmacologie, Faculté de Pharmacie, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France
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    • 1

      Battelle Europe, Neurochemistry–neuropharmacology, Pharmaceutical Research Group, 7, Route de Drize, 1227 Carouge-Genève, Switzerland

  • Jean-François Pujol,

    1. Université Claude Bernard et CNRS UMR 105, Laboratoire de Neuropharmacologie, Faculté de Pharmacie, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France
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  • Bernard Renaud

    1. Université Claude Bernard et CNRS UMR 105, Laboratoire de Neuropharmacologie, Faculté de Pharmacie, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France
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Cédric Vachette, as above

Abstract

The aim of the present work was to determine if noradrenergic neurons of the anterior and the posterior subregions of the locus coeruleus exhibit a difference in reactivity in response to sodium nitroprusside-induced arterial hypotension, and if the pharmacological induction of tyrosine hydroxylase by RU24722 modifies the reactivity of locus coeruleus neurons to this hypotensive stimulus. Previous findings have demonstrated that administration of RU24722 increases the concentration of tyrosine hydroxylase in the rat locus coeruleus by two different mechanisms in the anterior and in the posterior locus coeruleus subregions. The goal of the present study was to measure in vivo the changes in catecholaminergic metabolism in the locus coeruleus after treatment with RU24722 using differential normal pulse voltammetry (DNPV). In vehicle-treated rats, arterial hypotension increased catecholaminergic metabolism with the same pattern in the two locus coeruleus subregions. However, the changes in the magnitude of the catechol oxidation current throughout the recording period were significantly smaller in the posterior subregion (P < 0.001). In the RU24722-pretreated rats, there was a 39% increase in tyrosine hydroxylase and dihydroxyphenylacetic acid in the locus coeruleus. The functional reactivity to hypotension measured by DNPV was significantly decreased (P < 0.001) in both the anterior and posterior locus coeruleus subregions with RU24722 treatment. Therefore, this study suggests that the response of locus coeruleus cells to a hypotensive stimulus depends upon the intracellular tyrosine hydroxylase concentration both in the basal condition and during pharmacological induction of tyrosine hydroxylase gene expression.

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