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L-stepholidine reduced L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease.
Neurobiol Aging. 2010 Jun; 31(6):926-36.NA

Abstract

L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) remains a challenge in Parkinson's disease (PD) drug therapy. In the present study, we examined the effect of L-stepholidine (L-SPD), a known dual dopamine receptor agent, on LID in 6-hydroxydopamine (6-OHDA)-lesioned PD rat model. Daily administration of L-DOPA to PD rats for 22 days induced steady expression of LID, co-administration of L-SPD with L-DOPA significantly ameliorated LID without compromising the therapeutic potency of L-DOPA, indicating that L-SPD attenuated LID development. L-SPD alone elicited stable contralateral rotational behavior without inducing significant dyskinesia. Acute administration of L-SPD to rats with established LID produced significant relief of dyskinesia; this effect was mimicked by D(2) receptor antagonist haloperidol, but blunted by 5-HT(1A) receptor antagonist WAY100635. Furthermore, the mRNA level of 5-HT(1A) decreased significantly on 6-OHDA-lesioned striata, whereas chronic L-SPD treatment restored 5-HT(1A) receptor mRNA level on the lesioned striata. The present data demonstrated that L-SPD elicited antidyskinesia effects via both dopamine (D(2) receptor antagonistic activity) and nondopamine (5-HT(1A) agonistic activity) mechanisms.

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Authors+Show Affiliations

Mo J
State Key Laboratory of Drug Research, Department of Neuropharmacology, Shanghai Institute of Material Medica, Chinese Academy of Sciences, Shanghai, China.
Zhang H
No affiliation info available
Yu LP
No affiliation info available
Sun PH
No affiliation info available
Jin GZ
No affiliation info available
Zhen X
No affiliation info available

MeSH

8-Hydroxy-2-(di-n-propylamino)tetralinAnalysis of VarianceAnimalsAntiparkinson AgentsAntipsychotic AgentsBenzazepinesBerberineCHO CellsCorpus StriatumCricetinaeCricetulusDisease Models, AnimalDopamine AgentsDrug Administration ScheduleDrug InteractionsDyskinesiasGene Expression RegulationLevodopaMaleOxidopamineParkinsonian DisordersRNA, MessengerRatsRats, Sprague-DawleyReceptor, Serotonin, 5-HT1ASerotonin Receptor AgonistsTransfectionTritium

Pub Type(s)

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

Language

eng

PubMed ID

18707801

Citation

Mo, Jiao, et al. "L-stepholidine Reduced L-DOPA-induced Dyskinesia in 6-OHDA-lesioned Rat Model of Parkinson's Disease." Neurobiology of Aging, vol. 31, no. 6, 2010, pp. 926-36.
Mo J, Zhang H, Yu LP, et al. L-stepholidine reduced L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease. Neurobiol Aging. 2010;31(6):926-36.
Mo, J., Zhang, H., Yu, L. P., Sun, P. H., Jin, G. Z., & Zhen, X. (2010). L-stepholidine reduced L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease. Neurobiology of Aging, 31(6), 926-36. https://doi.org/10.1016/j.neurobiolaging.2008.06.017
Mo J, et al. L-stepholidine Reduced L-DOPA-induced Dyskinesia in 6-OHDA-lesioned Rat Model of Parkinson's Disease. Neurobiol Aging. 2010;31(6):926-36. PubMed PMID: 18707801.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - L-stepholidine reduced L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease. AU - Mo,Jiao, AU - Zhang,Hai, AU - Yu,Lei-Ping, AU - Sun,Pei-Hua, AU - Jin,Guo-Zhang, AU - Zhen,Xuechu, Y1 - 2008/08/15/ PY - 2007/11/19/received PY - 2008/05/27/revised PY - 2008/06/30/accepted PY - 2008/8/19/pubmed PY - 2010/7/14/medline PY - 2008/8/19/entrez SP - 926 EP - 36 JF - Neurobiology of aging JO - Neurobiol Aging VL - 31 IS - 6 N2 - L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) remains a challenge in Parkinson's disease (PD) drug therapy. In the present study, we examined the effect of L-stepholidine (L-SPD), a known dual dopamine receptor agent, on LID in 6-hydroxydopamine (6-OHDA)-lesioned PD rat model. Daily administration of L-DOPA to PD rats for 22 days induced steady expression of LID, co-administration of L-SPD with L-DOPA significantly ameliorated LID without compromising the therapeutic potency of L-DOPA, indicating that L-SPD attenuated LID development. L-SPD alone elicited stable contralateral rotational behavior without inducing significant dyskinesia. Acute administration of L-SPD to rats with established LID produced significant relief of dyskinesia; this effect was mimicked by D(2) receptor antagonist haloperidol, but blunted by 5-HT(1A) receptor antagonist WAY100635. Furthermore, the mRNA level of 5-HT(1A) decreased significantly on 6-OHDA-lesioned striata, whereas chronic L-SPD treatment restored 5-HT(1A) receptor mRNA level on the lesioned striata. The present data demonstrated that L-SPD elicited antidyskinesia effects via both dopamine (D(2) receptor antagonistic activity) and nondopamine (5-HT(1A) agonistic activity) mechanisms. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/18707801/L_stepholidine_reduced_L_DOPA_induced_dyskinesia_in_6_OHDA_lesioned_rat_model_of_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(08)00232-7 DB - PRIME DP - Unbound Medicine ER -