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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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Integrative Medical Biology, Umeå University, 901 87 Umeå, Sweden.
Department of Anatomy, Neurobiology, and Neurology, University of Kentucky Medical Center, Lexington, KY, USA.
Integrative 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.


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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