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Chronic SKF83959 induced less severe dyskinesia and attenuated L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease.
Neuropharmacology. 2007 Jul; 53(1):125-33.N

Abstract

SKF83959, a recently identified selective agonist of putative phosphoinositide-linked (PI-linked) D(1) dopamine (DA) receptor, is found to elicit excellent anti-parkinsonism effects in monkeys and rodents. In the present study, the effects of SKF83959 on L-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) were assessed in a unilateral 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease (PD). The results indicated that chronic L-DOPA (6 mg/kg) induced a progressive dyskinesia-like behavior in PD rats, whereas SKF83959 (0.5 mg/kg) elicited significantly less severe dyskinesia while exerts its anti-parkinsonian action effectively. Application of D(1) receptor, but not D(2), alpha or 5-HT receptor antagonist attenuated SKF83959-induced dyskinesia, indicating that a D(1) receptor-mediated events, assumed via PI-linked D(1) receptor. Interestingly, chronic co-administration of SKF83959 significantly reduced LID at no expanse of reduction in the anti-parkinsonian potency in PD rats. However, this anti-dyskinesia effect was not observed while SKF83959 was acutely administered in rats with established LID. This implies that chronic SKF83959 attenuated the development of dyskinesia. Immediate early gene FosB is previously reported to positively associate with dyskinesia. However, we found that the anti-dyskinesia effect of chronic SKF83959 was independent of FosB since SKF83959 produced stronger FosB expression in the lesioned striatum than that of L-DOPA while exerting its anti-dyskinesia action. The present data demonstrated that SKF83959 reduces LID by attenuating the development of dyskinesia; the underlying signaling pathway for the anti-dyskinesia action of SKF83959 appears not to depend on FosB.

Authors+Show Affiliations

Zhang H
Hubei Provincial Key Laboratory for Neural Diseases, Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Ma L
No affiliation info available
Wang F
No affiliation info available
Chen J
No affiliation info available
Zhen X
No affiliation info available

MeSH

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepineAnalysis of VarianceAnimalsDisease Models, AnimalDopamine AgonistsDopamine AntagonistsDrug Administration ScheduleDrug InteractionsDyskinesia, Drug-InducedLevodopaMaleMovementOxidopamineParkinson DiseaseProto-Oncogene Proteins c-fosRatsRats, Sprague-DawleySerotonin AntagonistsSpiperoneSympatholyticsTime Factors

Pub Type(s)

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

Language

eng

PubMed ID

17553535

Citation

Zhang, Hai, et al. "Chronic SKF83959 Induced Less Severe Dyskinesia and Attenuated L-DOPA-induced Dyskinesia in 6-OHDA-lesioned Rat Model of Parkinson's Disease." Neuropharmacology, vol. 53, no. 1, 2007, pp. 125-33.
Zhang H, Ma L, Wang F, et al. Chronic SKF83959 induced less severe dyskinesia and attenuated L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease. Neuropharmacology. 2007;53(1):125-33.
Zhang, H., Ma, L., Wang, F., Chen, J., & Zhen, X. (2007). Chronic SKF83959 induced less severe dyskinesia and attenuated L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease. Neuropharmacology, 53(1), 125-33.
Zhang H, et al. Chronic SKF83959 Induced Less Severe Dyskinesia and Attenuated L-DOPA-induced Dyskinesia in 6-OHDA-lesioned Rat Model of Parkinson's Disease. Neuropharmacology. 2007;53(1):125-33. PubMed PMID: 17553535.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic SKF83959 induced less severe dyskinesia and attenuated L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease. AU - Zhang,Hai, AU - Ma,Liqun, AU - Wang,Fang, AU - Chen,Jianguo, AU - Zhen,Xuechu, Y1 - 2007/04/29/ PY - 2007/02/05/received PY - 2007/04/04/revised PY - 2007/04/17/accepted PY - 2007/6/8/pubmed PY - 2007/11/10/medline PY - 2007/6/8/entrez SP - 125 EP - 33 JF - Neuropharmacology JO - Neuropharmacology VL - 53 IS - 1 N2 - SKF83959, a recently identified selective agonist of putative phosphoinositide-linked (PI-linked) D(1) dopamine (DA) receptor, is found to elicit excellent anti-parkinsonism effects in monkeys and rodents. In the present study, the effects of SKF83959 on L-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) were assessed in a unilateral 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease (PD). The results indicated that chronic L-DOPA (6 mg/kg) induced a progressive dyskinesia-like behavior in PD rats, whereas SKF83959 (0.5 mg/kg) elicited significantly less severe dyskinesia while exerts its anti-parkinsonian action effectively. Application of D(1) receptor, but not D(2), alpha or 5-HT receptor antagonist attenuated SKF83959-induced dyskinesia, indicating that a D(1) receptor-mediated events, assumed via PI-linked D(1) receptor. Interestingly, chronic co-administration of SKF83959 significantly reduced LID at no expanse of reduction in the anti-parkinsonian potency in PD rats. However, this anti-dyskinesia effect was not observed while SKF83959 was acutely administered in rats with established LID. This implies that chronic SKF83959 attenuated the development of dyskinesia. Immediate early gene FosB is previously reported to positively associate with dyskinesia. However, we found that the anti-dyskinesia effect of chronic SKF83959 was independent of FosB since SKF83959 produced stronger FosB expression in the lesioned striatum than that of L-DOPA while exerting its anti-dyskinesia action. The present data demonstrated that SKF83959 reduces LID by attenuating the development of dyskinesia; the underlying signaling pathway for the anti-dyskinesia action of SKF83959 appears not to depend on FosB. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/17553535/Chronic_SKF83959_induced_less_severe_dyskinesia_and_attenuated_L_DOPA_induced_dyskinesia_in_6_OHDA_lesioned_rat_model_of_Parkinson's_disease_ DB - PRIME DP - Unbound Medicine ER -