title: Effects of L-DOPA and STN-HFS dyskinesiogenic treatments on NR2B regulation in basal ganglia in the rat model of Parkinson's disease.
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: 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.
authors: Adrien
authors: A
authors: Quintana
authors: Véronique
authors: V
authors: Sgambato-Faure
authors: Marc
authors: M
authors: Savasta
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D046690:Deep Brain Stimulation / Q000009:adverse effects; D015259:Dopamine Agents / Q000009:adverse effects; D020820:Dyskinesias / Q000209:etiology* / Q000378:metabolism*; D004567:Electrodes, Implanted; D007150:Immunohistochemistry; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D020531:Subthalamic Nucleus / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa