Serotonergic nerve fibers in l-DOPA-derived dopamine release and dyskinesia

N. Nevalainen, S. Af Bjerkén, G. A. Gerhardt, I. Strömberg

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)73-86
Number of pages14
JournalNeuroscience
Volume260
DOIs
StatePublished - Feb 28 2014

Bibliographical note

Funding Information:
This study was funded by the Swedish Research Council Grant # 09917, The Umeå University Medical Faculty Funds, Konung Gustav V och drottning Victoria’s Fond, and Parkinsonfonden, Sweden. There are no conflicts of interest to be declared, neither financial nor personal.

Keywords

  • 5-HT
  • Dyskinesia
  • Fluoxetine
  • In vivo chronoamperometry
  • L-DOPA
  • WAY-100 635

ASJC Scopus subject areas

  • General Neuroscience

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