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Effects of L-DOPA and STN-HFS dyskinesiogenic treatments on NR2B regulation in basal ganglia in the rat model of Parkinson's disease.
- Source :
-
Neurobiology of disease [Neurobiol Dis] 2012 Dec; Vol. 48 (3), pp. 379-90. Date of Electronic Publication: 2012 Jun 30. - Publication Year :
- 2012
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Abstract
- 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 1h, 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 Tyr1472 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.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Deep Brain Stimulation adverse effects
Dopamine Agents adverse effects
Electrodes, Implanted
Immunohistochemistry
Levodopa adverse effects
Male
Parkinsonian Disorders therapy
Rats
Rats, Sprague-Dawley
Subthalamic Nucleus metabolism
Basal Ganglia metabolism
Dyskinesias etiology
Dyskinesias metabolism
Parkinsonian Disorders metabolism
Receptors, N-Methyl-D-Aspartate metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-953X
- Volume :
- 48
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neurobiology of disease
- Publication Type :
- Academic Journal
- Accession number :
- 22759925
- Full Text :
- https://doi.org/10.1016/j.nbd.2012.06.009