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Combined 5-HT1A and...
Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia.
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- Munoz, Ana (author)
- Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups
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Li, Qin (author)
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Gardoni, Fabrizio (author)
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Marcello, Elena (author)
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Qin, Chuan (author)
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- Carlsson, Thomas (author)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Kirik, Deniz (author)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
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Luca, Monica Di (author)
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- Björklund, Anders (author)
- Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups
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Bezard, Erwan (author)
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- Carta, Manolo (author)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Neurobiologi,Lund University Research Groups,Neurobiology
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(creator_code:org_t)
- 2008-10-24
- 2008
- English.
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In: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 131, s. 3380-3394
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https://doi.org/10.1...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- L-DOPA
- Dyskinesia
- Serotonin agonists
- Parkinson's disease
- MPTP
- monkeys
Publication and Content Type
- art (subject category)
- ref (subject category)
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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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show more...
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Kirik, Deniz
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Luca, Monica Di
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Björklund, Ander ...
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Bezard, Erwan
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Carta, Manolo
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Neurology
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Brain
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Lund University