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Serotonergic nerve ...
Serotonergic nerve fibers in l-DOPA-derived dopamine release and dyskinesia
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- Nevalainen, Nina (author)
- Umeå universitet,Histologi med cellbiologi,nina.nevalainen@diagrad.umu.se
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- Af Bjerkén, Sara (author)
- Umeå universitet,Histologi med cellbiologi
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- Gerhardt, G A (author)
- Department of Anatomy, Neurobiology, and Neurology, University of Kentucky Medical Center, Lexington, KY, USA
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- Strömberg, Iingrid (author)
- Umeå universitet,Histologi med cellbiologi
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(creator_code:org_t)
- Elsevier, 2014
- 2014
- English.
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In: Neuroscience. - : Elsevier. - 0306-4522 .- 1873-7544. ; 260, s. 73-86
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The 5-HT (5-hydroxytryptamine) system has been assigned a key role in the development of 3,4-dihydroxyphenyl-l-alanine (l-DOPA)-induced dyskinesia, mainly due to 5-HT neuronal ability to decarboxylate l-DOPA into dopamine. Nevertheless, knowledge of l-DOPA-induced events that could lead to development of dyskinesias are limited and therefore the present work has evaluated (i) the role of the 5-HT system in l-DOPA-derived dopamine synthesis when dopamine neurons are present, (ii) l-DOPA-induced effects on striatal dopamine release and clearance, and on 5-HT nerve fiber density, and (iii) the behavioral outcome of altered 5-HT transmission in dyskinetic rats. Chronoamperometric recordings demonstrated attenuated striatal l-DOPA-derived dopamine release (∼30%) upon removal of 5-HT nerve fibers in intact animals. Interestingly, four weeks of daily l-DOPA treatment yielded similar-sized dopamine peak amplitudes in intact animals as found after a 5-HT-lesion. Moreover, chronic l-DOPA exposure attenuated striatal 5-HT nerve fiber density in the absence of dopamine nerve terminals. Furthermore, fluoxetine-induced altered 5-HT transmission blocked dyskinetic behavior via action on 5-HT1A receptors. Taken together, the results indicate a central role for the 5-HT system in l-DOPA-derived dopamine synthesis and in dyskinesia, and therefore potential l-DOPA-induced deterioration of 5-HT function might reduce l-DOPA efficacy as well as promote the upcoming of motor side effects.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Keyword
- l-DOPA
- dyskinesia
- 5-HT
- in vivo chronoamperometry
- fluoxetine
- WAY-100 635
Publication and Content Type
- ref (subject category)
- art (subject category)
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