RGD Reference Report - l-Stepholidine reduced l-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease. - Rat Genome Database

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l-Stepholidine reduced l-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease.

Authors: Mo, J  Zhang, H  Yu, LP  Sun, PH  Jin, GZ  Zhen, X 
Citation: Mo J, etal., Neurobiol Aging. 2008 Aug 14.
RGD ID: 2311579
Pubmed: PMID:18707801   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neurobiolaging.2008.06.017   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DRD2HumanDrug-Induced Dyskinesia  ISODrd2 (Rattus norvegicus) RGD 
Drd2RatDrug-Induced Dyskinesia  IDA  RGD 
Drd2MouseDrug-Induced Dyskinesia  ISODrd2 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Drd2  (dopamine receptor D2)

Genes (Mus musculus)
Drd2  (dopamine receptor D2)

Genes (Homo sapiens)
DRD2  (dopamine receptor D2)


Additional Information