QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, February 28, 2007, 27(9):2377-2386; doi:10.1523/JNEUROSCI.2949-06.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Oueslati, A. Articles by Salin, P. Search for Related Content PubMed PubMed Citation Articles by Oueslati, A. Articles by Salin, P.

 Previous Article  |  Next Article 

Neurobiology of Disease
High-Frequency Stimulation of the Subthalamic Nucleus Potentiates L-DOPA-Induced Neurochemical Changes in the Striatum in a Rat Model of Parkinson's Disease

Abid Oueslati,¹ Véronique Sgambato-Faure,^2,3 Christophe Melon,¹ Philippe Kachidian,¹ Paolo Gubellini,¹ Mohammed Amri,⁴ Lydia Kerkerian-Le Goff,¹ and Pascal Salin¹

¹Developmental Biology Institute of Marseille Luminy, Unité Mixte de Recherche 6216, Centre National de la Recherche Scientifique–Université de la Méditerranée, 13402 Marseille cedex 20, France, ²Neurosciences Précliniques, Institut National de la Santé et de la Recherche Médicale U318, 38043 Grenoble cedex, France, ³Dynamique des Réseaux Neuronaux, Institut National de la Santé et de la Recherche U704–Université Joseph Fourier, 38041 Grenoble Cedex 9, France, and ⁴Laboratoire de Physiologie de la Nutrition, Faculté des Sciences de Tunis, 2092 El Manar, Tunis, Tunisia

Correspondence should be addressed to Pascal Salin, Team "Cellular Interactions, Neurodegeneration and Neuroplasticity," Developmental Biology Institute of Marseille Luminy, Unité Mixte de Recherche 6216, Centre National de la Recherche Scientifique–Université de la Méditerranée, 31 chemin Joseph Aiguier, 13402 Marseille cedex 20, France. Email: salin{at}ibdml.univ-mrs.fr

This study examined the cellular changes produced in the striatum by chronic L-DOPA treatment and prolonged subthalamic nucleus high-frequency stimulation (STN–HFS) applied separately, successively, or in association, in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease (PD). Only animals showing severe L-DOPA-induced dyskinesias (LIDs) were included, and STN–HFS was applied for 5 d at an intensity efficient for alleviating akinesia without inducing dyskinesias. L-DOPA treatment alone induced FosB/FosB immunoreactivity, exacerbated the postlesional increase in preproenkephalin, reversed the decrease in preprotachykinin, and markedly increased mRNA levels of preprodynorphin and of the glial glutamate transporter GLT1, which were respectively decreased and unaffected by the dopamine lesion. STN–HFS did not affect per se the postlesion changes in any of these markers. However, when applied in association with L-DOPA treatment, it potentiated the positive modulation exerted by L-DOPA on all of the markers examined and tended to exacerbate LIDs. After 5 d of L-DOPA withdrawal, the only persisting drug-induced responses were an elevation in preprodynorphin mRNA levels and in the number of FosB/FosB-immunoreactive neurons. Selective additional increases in these two markers were measured when STN–HFS was applied subsequently to L-DOPA treatment. These data provide the first evidence that STN–HFS exacerbates the responsiveness of striatal cells to L-DOPA medication and suggest that STN–HFS acts specifically through an L-DOPA-modulated signal transduction pathway associated with LIDs in the striatum. They point to striatal cells as a primary site for the complex interactions between these two therapeutic approaches in PD and argue against a direct anti-dyskinetic action of STN–HFS.

Key words: deep brain stimulation; L-DOPA; dyskinesias; neuropeptides; FosB; GLT1; motor cortex

---

Received July 12, 2006; revised Jan. 25, 2007; accepted Jan. 27, 2007.

Correspondence should be addressed to Pascal Salin, Team "Cellular Interactions, Neurodegeneration and Neuroplasticity," Developmental Biology Institute of Marseille Luminy, Unité Mixte de Recherche 6216, Centre National de la Recherche Scientifique–Université de la Méditerranée, 31 chemin Joseph Aiguier, 13402 Marseille cedex 20, France. Email: salin{at}ibdml.univ-mrs.fr

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help