Dopamine release from serotonergic nerve fibers is reduced in L-DOPA-induced dyskinesia |
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Authors: | Nevalainen Nina Af Bjerkén Sara Lundblad Martin Gerhardt Greg A Strömberg Ingrid |
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Affiliation: | 1. Integrative Medical Biology, Ume? University, Ume?, Sweden;2. Basal Ganglia Pathophysiology Unit, Neuroscience Section, Department of Experimental Medical Science, Lund University, Lund, Sweden;3. Anatomy, Neurobiology, and Neurology, University of Kentucky Med Center, Lexington, KY, USA |
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Abstract: | L-DOPA is the most commonly used treatment for symptomatic control in patients with Parkinson's disease. Unfortunately, most patients develop severe side-effects, such as dyskinesia, upon chronic l-DOPA treatment. The patophysiology of dyskinesia is unclear; however, involvement of serotonergic nerve fibers in converting l-DOPA to dopamine has been suggested. Therefore, potassium-evoked dopamine release was studied after local application of l-DOPA in the striata of normal, dopamine- and dopamine/serotonin-lesioned l-DOPA na?ve, and dopamine-denervated chronically l-DOPA-treated dyskinetic rats using in vivo chronoamperometry. The results revealed that local l-DOPA administration into normal and intact hemisphere of dopamine-lesioned l-DOPA na?ve animals significantly increased the potassium-evoked dopamine release. l-DOPA application also increased the dopamine peak amplitude in the dopamine-depleted l-DOPA na?ve striatum, although these dopamine levels were several-folds lower than in the normal striatum, whereas no increased dopamine release was found in the dopamine/serotonin-denervated striatum. In dyskinetic animals, local l-DOPA application did not affect the dopamine release, resulting in significantly attenuated dopamine levels compared with those measured in l-DOPA na?ve dopamine-denervated striatum. To conclude, l-DOPA is most likely converted to dopamine in serotonergic nerve fibers in the dopamine-depleted striatum, but the dopamine release is several-fold lower than in normal striatum. Furthermore, l-DOPA loading does not increase the dopamine release in dyskinetic animals as found in l-DOPA na?ve animals, despite similar density of serotonergic innervation. Thus, the dopamine overflow produced from the serotonergic nerve fibers appears not to be the major cause of dyskinetic behavior. |
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Keywords: | 5‐HT chronoamperometry l‐DOPA‐induced dyskinesia SERT |
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