Journal
NEUROBIOLOGY OF DISEASE
Volume 48, Issue 3, Pages 379-390Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2012.06.009
Keywords
Parkinson's disease; Dyskinesia; 6-OHBA lesion; L-DOPA; High-frequency stimulation; Glutamate; NMDA receptors; NR2B; Basal ganglia
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Funding
- Institut National de la Sante et de la Recherche Medicale
- le Ministere de la Recherche et des Nouvelles Technologies (Agence Nationale pour la Recherche) [ANR-05-NEUR-013-01]
- Region Rhone-Alpes [11]
- Association France Parkinson
- Fondation NRJ-Institut de France
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Dyskinesia is a major side effect of chronic levodopa (L-DOPA) administration, the reference treatment for Parkinson's disease (PD). High-frequency stimulation of the subthalamic nucleus (STN-HFS) alleviates parkinsonian motor symptoms and indirectly improves dyskinesia by decreasing L-DOPA requirement. However, inadequate stimulation can also trigger dyskinetic movements in PD patients and animal models. Here, we investigated the possible association between L-DOPA- and STN-HFS-induced dyskinesia and regulation of the NR2B subunit of NMDA receptors in the rodent model of PD. We subjected 6-OHDA-lesioned rats to HFS for 1 h, at an intensity triggering forelimb dyskinesia. Other 6-OHDA-lesioned rats were treated with chronic high doses of L-DOPA for ten days, to induce abnormal involuntary movements. The 6-OHDA lesion regulated NR2B only in the SNr, where the activation of NR2B was observed (as assessed by phosphorylation of the Tyr(1472) residue). Both STN-HFS and L-DOPA dyskinesiogenic treatments induced NR2B activation in the STN and EP, but only L-DOPA triggered NR2B hyperphosphorylation in the striatum. Finally, the use of CP-101,606 exacerbated L-DOPA-induced motor behavior and associated NR2B hyperphosphorylation in the striatum. STN and EP. Thus. NR2B activation in basal ganglia structures is correlated with dyskinesia. (c) 2012 Elsevier Inc. All rights reserved.
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