Sökning: WFRF:(Munoz Ana)
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Combined 5-HT1A and...
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Munoz, AnaLund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups
(författare)
Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia.
- Artikel/kapitelEngelska2008
Förlag, utgivningsår, omfång ...
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2008-10-24
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Oxford University Press (OUP),2008
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:83b2fe99-549f-4bbd-b750-fc7ec81dc032
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https://lup.lub.lu.se/record/1261923URI
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https://doi.org/10.1093/brain/awn235DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
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Appearance of dyskinesia is a common problem of long-term l-DOPA treatment in Parkinson's disease patients and represents a major limitation for the pharmacological management of the motor symptoms in advanced disease stages. We have recently demonstrated that dopamine released from serotonin neurons is responsible for l-DOPA-induced dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats, raising the possibility that blockade of serotonin neuron activity by combination of 5-HT(1A) and 5-HT(1B) agonists could reduce l-DOPA-induced dyskinesia. In the present study, we have investigated the efficacy of 5-HT(1A) and 5-HT(1B) agonists to counteract l-DOPA-induced dyskinesia in 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-treated macaques, the gold standard model of Parkinson's disease. In addition, we have studied the ability of this treatment to prevent development of l-DOPA-induced dyskinesia in 6-OHDA-lesioned rats. The results demonstrate the existence of a potent synergistic effect between 5-HT(1A) and 5-HT(1B) agonists in their ability to dampen l-DOPA-induced dyskinesia in the MPTP-treated macaques. Sub-threshold doses of the drugs, which individually produced no effect, were able to reduce the abnormal involuntary movements by up to 80% when administered in combination, without affecting the anti-parkinsonian properties of l-DOPA. Furthermore, chronic administration of low doses of the 5-HT(1) agonists in combination was able to prevent development of dyskinesia, and reduce the up-regulation of FosB after daily treatment with l-DOPA in the rat 6-OHDA model. Our results support the importance of a clinical investigation of the effect of 5-HT(1A) and 5-HT(1B) agonists, particularly in combination, in dyskinetic l-DOPA-treated Parkinson's disease patients.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Li, Qin
(författare)
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Gardoni, Fabrizio
(författare)
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Marcello, Elena
(författare)
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Qin, Chuan
(författare)
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Carlsson, ThomasLund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)mphy-tka
(författare)
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Kirik, DenizLund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)mphy-dki
(författare)
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Luca, Monica Di
(författare)
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Björklund, AndersLund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups(Swepub:lu)mphy-abj
(författare)
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Bezard, Erwan
(författare)
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Carta, ManoloLund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Neurobiologi,Lund University Research Groups,Neurobiology(Swepub:lu)med-mca
(författare)
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NeurobiologiForskargrupper vid Lunds universitet
(creator_code:org_t)
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Ingår i:Brain: Oxford University Press (OUP)131, s. 3380-33941460-21560006-8950
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Munoz, Ana
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Li, Qin
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Gardoni, Fabrizi ...
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Marcello, Elena
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Qin, Chuan
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Carlsson, Thomas
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Kirik, Deniz
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Luca, Monica Di
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Bezard, Erwan
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Carta, Manolo
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