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: Lin-Lin Yin, Xing-Chao Geng, Xing-Zu Zhu
• Journal: Brain research bulletin (Brain Res Bull) Vol. 86 Issue 5-6 Pg. 367-72 (Nov 25 2011) ISSN: 1873-2747 [Electronic] United States
• PMID: 21963945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antiparkinson Agents
• Dopamine Agents
• RGS Proteins
• Receptors, Dopamine D1
• Receptors, Dopamine D2
• regulator of g-protein signaling 9
• Levodopa
• Benserazide
• Oxidopamine
• Apomorphine

Topics

• Animals
• Antiparkinson Agents (pharmacology, toxicity)
• Apomorphine (pharmacology)
• Behavior, Animal (drug effects)
• Benserazide (therapeutic use)
• Disease Models, Animal
• Dopamine Agents (pharmacology, toxicity)
• Dyskinesia, Drug-Induced (physiopathology)
• Levodopa (pharmacology, toxicity)
• Male
• Motor Activity (drug effects)
• Oxidopamine
• Parkinson Disease, Secondary (chemically induced, drug therapy, physiopathology)
• RGS Proteins (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Dopamine D1 (metabolism)
• Receptors, Dopamine D2 (metabolism)