L-stepholidine reduced L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease

Neurobiology of Aging
Jiao MoXuechu Zhen

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) m...Continue Reading

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Citations

Jan 5, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Jian Yu WangChun Fu Wu
Jul 2, 2015·Journal of Chemical Information and Modeling·Peng LianWei Fu
Jan 4, 2012·Journal of Ethnopharmacology·Ju-Xian SongYan-Bo Zhang
Sep 16, 2014·Parkinsonism & Related Disorders·Bing HanHua Zhao
Sep 4, 2012·Neurochemistry International·Golnasim RiahiThérèse Di Paolo
Dec 6, 2016·Expert Review of Neurotherapeutics·Hugo GeertsPatrick Roberts
Jun 6, 2018·Frontiers in Molecular Neuroscience·Di-Sheng LuFeng Zhang

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