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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.
Neurobiol Dis. 2012 Dec; 48(3):379-90.ND

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.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, France.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22759925

Citation

Quintana, Adrien, et al. "Effects of L-DOPA and STN-HFS Dyskinesiogenic Treatments On NR2B Regulation in Basal Ganglia in the Rat Model of Parkinson's Disease." Neurobiology of Disease, vol. 48, no. 3, 2012, pp. 379-90.
Quintana A, Sgambato-Faure V, Savasta M. Effects of L-DOPA and STN-HFS dyskinesiogenic treatments on NR2B regulation in basal ganglia in the rat model of Parkinson's disease. Neurobiol Dis. 2012;48(3):379-90.
Quintana, A., Sgambato-Faure, V., & Savasta, M. (2012). Effects of L-DOPA and STN-HFS dyskinesiogenic treatments on NR2B regulation in basal ganglia in the rat model of Parkinson's disease. Neurobiology of Disease, 48(3), 379-90. https://doi.org/10.1016/j.nbd.2012.06.009
Quintana A, Sgambato-Faure V, Savasta M. Effects of L-DOPA and STN-HFS Dyskinesiogenic Treatments On NR2B Regulation in Basal Ganglia in the Rat Model of Parkinson's Disease. Neurobiol Dis. 2012;48(3):379-90. PubMed PMID: 22759925.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of L-DOPA and STN-HFS dyskinesiogenic treatments on NR2B regulation in basal ganglia in the rat model of Parkinson's disease. AU - Quintana,Adrien, AU - Sgambato-Faure,Véronique, AU - Savasta,Marc, Y1 - 2012/06/30/ PY - 2012/03/02/received PY - 2012/06/06/revised PY - 2012/06/22/accepted PY - 2012/7/5/entrez PY - 2012/7/5/pubmed PY - 2013/5/1/medline SP - 379 EP - 90 JF - Neurobiology of disease JO - Neurobiol Dis VL - 48 IS - 3 N2 - 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. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/22759925/Effects_of_L_DOPA_and_STN_HFS_dyskinesiogenic_treatments_on_NR2B_regulation_in_basal_ganglia_in_the_rat_model_of_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(12)00224-0 DB - PRIME DP - Unbound Medicine ER -