Evidence for a role of the 5-HT1B receptor and its adaptor protein, p11, in L-DOPA treatment of an animal model of Parkinsonism
2008 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, Vol. 105, no 6, 2163-2168 p.Article in journal (Refereed) Published
Parkinson's disease (PD) is characterized by a progressive degeneration of substantia nigra dopaminergic neurons projecting to the striatum. Restoration of dopamine transmission by L-DOPA relieves symptoms of PD but causes prominent side effects. There is a strong serotonin innervation of the striatum by serotonergic neurons that remains relatively preserved in PD. The study of this innervation has been largely neglected. Here, we demonstrate that chronic L-DOPA administration to 6-OHDA-lesioned rodents increases, via D1 receptors, the levels of the 5-HT1B receptor and its adaptor protein, p11, in dopamine-denervated striatonigral neurons. Using unilaterally 6-OHDA-lesioned p11 WT and KO mice, it was found that administration of a selective 5-HT1B receptor agonist, CP94253, inhibited L-DOPA-induced rotational behavior and abnormal involuntary movements in a p11-dependent manner. These data reveal an L-DOPA-induced negative-feedback mechanism, whereby the serotonin system may influence the symptomatology of Parkinsonism.
Place, publisher, year, edition, pages
2008. Vol. 105, no 6, 2163-2168 p.
annexin II light chain, basal ganglia, Parkinson's disease, S100a10, serotonin
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-109765DOI: 10.1073/pnas.0711839105ISI: 000253261900070PubMedID: 18256188OAI: oai:DiVA.org:uu-109765DiVA: diva2:273924