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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.: NR2B hyperphosphorylation driven by L-DOPA and STN-HFS

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 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.
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https://www.hal.inserm.fr/inserm-00742517
Contributor : Marc Savasta <>
Submitted on : Tuesday, October 16, 2012 - 3:23:36 PM
Last modification on : Friday, November 6, 2020 - 3:51:34 AM
Long-term archiving on: : Thursday, January 17, 2013 - 11:36:17 AM

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Adrien Quintana, Véronique Sgambato-Faure, Marc Savasta. Effects of L-DOPA and STN-HFS dyskinesiogenic treatments on NR2B regulation in basal ganglia in the rat model of Parkinson's disease.: NR2B hyperphosphorylation driven by L-DOPA and STN-HFS. Neurobiology of Disease, Elsevier, 2012, 48 (3), pp.379-90. ⟨10.1016/j.nbd.2012.06.009⟩. ⟨inserm-00742517⟩

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