Serotonergic nerve fibers in l-DOPA-derived dopamine release and dyskinesia
2014 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 260, 73-86 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Elsevier, 2014. Vol. 260, 73-86 p.
l-DOPA, dyskinesia, 5-HT, in vivo chronoamperometry, fluoxetine, WAY-100 635
Neurosciences Other Basic Medicine
IdentifiersURN: urn:nbn:se:umu:diva-84741DOI: 10.1016/j.neuroscience.2013.12.029ISI: 000330598100007PubMedID: 24361918OAI: oai:DiVA.org:umu-84741DiVA: diva2:689063