title: The involvement of RGS9 in l-3,4-dihydroxyphenylalanine-induced dyskinesias in unilateral 6-OHDA lesion rat model.
abstract: Chronic dopamine (DA) replacement therapy with L-3,4-dihydroxyphenylalanine (L-DOPA) in Parkinson's disease (PD) often leads to abnormal involuntary movements (AIMs) known as L-DOPA-induced dyskinesia (LID), mediated by DA receptors. However, mechanisms underlying LID occurrence are still unclear. Regulator of G-protein signaling RGS9, a member of the RGS family of GTPase accelerating proteins, is expressed specifically in the striatum, has been reported participated in LID. L-DOPA-induced AIMs can be modeled in rats with 6-hydroxydopamine (6-OHDA) lesions by chronic injection of L-DOPA. Herein, we compared the rotational responses and AIMs in 6-OHDA lesioned rats with L-DOPA/benserazide (10/2.5 mg/kg, once per day, i.p.) administration for 14 days whereas control animals received injections of saline. Furthermore, whether sub-chronic L-DOPA treatment impact RGS9 mRNA or protein expression in 6-OHDA lesion rats were also evaluated. As results shown, rotational behavior was not increased significantly, while an obvious AIMs were observed in rats with L-DOPA/benserazide (10/2.5mg/kg, i.p.) administration sub-chronically. In addition, expressions of RGS9 protein or mRNA analyzed by Western blot or real-time PCR with striatal extracts increased significantly after L-DOPA/benserazide. These data demonstrate that RGS9 expression can be modulated by sub-chronic L-DOPA/benserazide administration and increased RGS9 expression in striatum may be one of the reasons for the side effects such as dyskinesia induced by L-DOPA therapy.
authors.affiliation: Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory for Neurodegenerative Disease of Ministry of Education, 45 Changchun Street, Beijing 100053, PR China. yinll913@126.com
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Yin
authors.forename: Xing-Chao
authors.initials: XC
authors.lastname: Geng
authors.forename: Xing-Zu
authors.initials: XZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000633:toxicity*; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001545:Benserazide / Q000627:therapeutic use; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology / Q000633:toxicity*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D007980:Levodopa / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D015259:Dopamine Agents; D020710:RGS Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C116925:regulator of g-protein signaling 9; D007980:Levodopa; D001545:Benserazide; D016627:Oxidopamine; D001058:Apomorphine