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High-frequency stimulation of the subthalamic nucleus prolongs the increase in striatal dopamine induced by acute l-3,4-dihydroxyphenylalanine in dopaminergic denervated rats

Authors

  • Emilie Lacombe,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement,
    2. Université Joseph Fourier and
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  • Carole Carcenac,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement,
    2. Université Joseph Fourier and
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  • Sabrina Boulet,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement,
    2. Université Joseph Fourier and
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  • Claude Feuerstein,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement,
    2. Université Joseph Fourier and
    3. Centre Hospitalier Universitaire de Grenoble, Grenoble, France
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  • Anne Bertrand,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement,
    2. Université Joseph Fourier and
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  • Annie Poupard,

    1. Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement,
    2. Université Joseph Fourier and
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  • Marc Savasta

    1. Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement,
    2. Université Joseph Fourier and
    3. Centre Hospitalier Universitaire de Grenoble, Grenoble, France
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Dr Marc Savasta, Dynamique des Réseaux Neuroneaux du Mouvement, Institut National de la Santé et de la Recherche Médicale, Unité 836 (ex Unité 704), Université Joseph Fourier, Domaine Universitaire, 2280 rue de la Piscine, BP 53, 38041 Grenoble Cedex 09, France.
E-mail: marc.savasta@ujf-grenoble.fr

Abstract

High-frequency stimulation of the subthalamic nucleus (STN-HFS) is a powerful approach for treating the motor symptoms of Parkinson's disease (PD). It results in clinical improvement in patients with PD, further reducing the l-3,4-dihydroxyphenylalanine (L-DOPA) requirement and thus L-DOPA-induced dyskinesia. However, it remains unclear how STN-HFS modifies the response to L-DOPA. We investigated the effect of STN-HFS on striatal extracellular concentrations of dopamine and its metabolites following acute L-DOPA administration in intact or partially dopaminergic denervated (DA-PL) rats. L-DOPA treatment significantly increased striatal dopamine levels in intact and DA-PL animals, with the maximal effect observed 1 h after L-DOPA injection. This increase was more pronounced in DA-PL rats (ipsilateral to the lesion) than in intact animals. It remained fairly stable 1 h after the maximal effect of L-DOPA and then decreased towards basal values. STN-HFS in intact rats had no effect on the maximal L-DOPA-induced increase in striatal extracellular dopamine concentration or the return to basal values, the profiles observed being similar to those for non-stimulated intact animals. Conversely, STN-HFS amplified the L-DOPA-induced increase in striatal dopamine levels during the stimulation period (1 h) in DA-PL rats and this increase was sustained throughout the post-stimulation period (2.5 h), without the return to basal levels observed in stimulated intact and non-stimulated rats. These new neurochemical data suggest that STN-HFS interferes with L-DOPA effects, probably synergically, by stabilizing dopamine levels in the striatum and shed light on the mechanisms of STN-HFS in PD.

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