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Effects of high frequency stimulation of subthalamic nucleus on extracellular glutamate and GABA in substantia nigra and globus pallidus in the normal rat

Authors

  • François Windels,

    1. Equipe Neurochimie et Neuroplasticité Fonctionnelles, INSERM U.318 – Neurosciences Précliniques, Université Joseph Fourier, Pavillon de Neurologie, CHU de Grenoble, 38043 Grenoble Cedex 09, France
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  • Nicolas Bruet,

    1. Equipe Neurochimie et Neuroplasticité Fonctionnelles, INSERM U.318 – Neurosciences Précliniques, Université Joseph Fourier, Pavillon de Neurologie, CHU de Grenoble, 38043 Grenoble Cedex 09, France
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  • Annie Poupard,

    1. Equipe Neurochimie et Neuroplasticité Fonctionnelles, INSERM U.318 – Neurosciences Précliniques, Université Joseph Fourier, Pavillon de Neurologie, CHU de Grenoble, 38043 Grenoble Cedex 09, France
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  • Nadia Urbain,

    1. Laboratoire de Neuropharmacologie et Neurochimie, INSERM U.512, Université Claude Bernard, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France
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  • Guy Chouvet,

    1. Laboratoire de Neuropharmacologie et Neurochimie, INSERM U.512, Université Claude Bernard, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France
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  • Claude Feuerstein,

    1. Equipe Neurochimie et Neuroplasticité Fonctionnelles, INSERM U.318 – Neurosciences Précliniques, Université Joseph Fourier, Pavillon de Neurologie, CHU de Grenoble, 38043 Grenoble Cedex 09, France
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  • Marc Savasta

    1. Equipe Neurochimie et Neuroplasticité Fonctionnelles, INSERM U.318 – Neurosciences Précliniques, Université Joseph Fourier, Pavillon de Neurologie, CHU de Grenoble, 38043 Grenoble Cedex 09, France
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: Dr Marc Savasta, as above.
E-mail: marc.savasta@ujf-grenoble.fr

Abstract

High frequency stimulation (130 Hz) of the subthalamic nucleus has dramatic beneficial motor effects in severe parkinsonian patients. However, the mechanisms underlying these clinical results remain obscure. The objective of the present work was to study the neurochemical changes induced in rats by high frequency stimulation of the subthalamic nucleus by using intracerebral microdialysis within its target structures. Our results show that high frequency stimulation of the subthalamic nucleus induces a significant increase of extracellular glutamate levels in the ipsilateral globus pallidus and substantia nigra while GABA was augmented only in the substantia nigra. These data suggest that functional effects induced by high frequency stimulation of the subthalamic nucleus might imply distal mechanisms involving the synaptic relationships with the subthalamic efferences. They question the current view that the direct inhibition of the subthalamic neurons is induced by high frequency stimulation.

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