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Evidence for a role of the 5-HT1B receptor and its adaptor protein, p11, in L-DOPA treatment of an animal model of Parkinsonism
Karolinska Institutet, Institutionen för fysiologi och farmakologi. (Translationell neurofarmakologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, MMS, Medical Mass Spectrometry.
The Rockefeller University, Laboratory of Molecular and Cellular Neuroscience.
Karolinska Institutet, Institutionen för fysiologi och farmakologi. (Translationell neurofarmakologi)
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
Abstract [en]

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.
Keyword [en]
annexin II light chain, basal ganglia, Parkinson's disease, S100a10, serotonin
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-109765DOI: 10.1073/pnas.0711839105ISI: 000253261900070PubMedID: 18256188OAI: oai:DiVA.org:uu-109765DiVA: diva2:273924
Available from: 2009-10-26 Created: 2009-10-26 Last updated: 2010-01-13Bibliographically approved

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