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Forelimb dyskinesia mediated by high-frequency stimulation of the subthalamic nucleus is linked to rapid activation of the NR2B subunit of N-methyl-D-aspartate receptors.

Adrien Quintana 1 Christophe Melon 2 Lydia Kerkerian-Le Goff 2 Pascal Salin 2 Marc Savasta 1, * Véronique Sgambato-Faure 3
* Corresponding author
3 INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement
CNC - Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229, GIN - Grenoble Institut des Neurosciences
Abstract : Dyskinesia is a major side-effect of chronic l-DOPA administration, the reference treatment for Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN-HFS) alleviates parkinsonian motor symptoms and indirectly improves dyskinesia by decreasing the L-DOPA requirement. However, inappropriate stimulation can also trigger dyskinetic movements, in both human and rodents. We investigated whether STN-HFS-evoked forelimb dyskinesia involved changes in glutamatergic neurotransmission as previously reported for L-DOPA-induced dyskinesias, focusing on the role of NR2B-containing N-methyl-D-aspartate receptors (NR2B/NMDARs). We applied STN-HFS in normal rats at intensities above and below the threshold for triggering forelimb dyskinesia. Dyskinesiogenic STN-HFS induced the activation of NR2B (as assessed by immunodetection of the phosphorylated residue Tyr(1472)) in neurons of the subthalamic nucleus, entopeduncular nucleus, motor thalamus and forelimb motor cortex. The severity of STN-HFS-induced forelimb dyskinesia was decreased in a dose-dependent manner by systemic injections of CP-101,606, a selective blocker of NR2B/NMDARs, but was either unaffected or increased by the non-selective N-methyl-D-aspartate receptor antagonist, MK-801.
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Adrien Quintana, Christophe Melon, Lydia Kerkerian-Le Goff, Pascal Salin, Marc Savasta, et al.. Forelimb dyskinesia mediated by high-frequency stimulation of the subthalamic nucleus is linked to rapid activation of the NR2B subunit of N-methyl-D-aspartate receptors.. European Journal of Neuroscience, Wiley, 2010, 32 (3), pp.423-34. ⟨10.1111/j.1460-9568.2010.07290.x⟩. ⟨inserm-00627991⟩

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