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Neuroscience. 2014 Feb 28;260:73-86. doi: 10.1016/j.neuroscience.2013.12.029. Epub 2013 Dec 18.

Serotonergic nerve fibers in L-DOPA-derived dopamine release and dyskinesia.

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  • 1Integrative Medical Biology, Umeå University, 901 87 Umeå, Sweden.
  • 2Department of Anatomy, Neurobiology, and Neurology, University of Kentucky Medical Center, Lexington, KY, USA.
  • 3Integrative Medical Biology, Umeå University, 901 87 Umeå, Sweden. Electronic address:


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.

Copyright © 2013 IBRO. All rights reserved.


5,7-DHT; 5,7-dihydroxytryptamine; 5-HT; 6-OHDA; 6-hydroxydopamine; AIM; ANOVA; LGE; LID; PBS; SERT; Serotonin; TH; WAY-100 635; abnormal involuntary movement; analysis of variance; dyskinesia; fluoxetine; in vivo chronoamperometry; l-DOPA; l-DOPA-induced dyskinesia; lateral ganglionic eminence; phosphate-buffered saline; serotonin transporter; tyrosine hydroxylase

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