title: Dopamine release from serotonergic nerve fibers is reduced in L-DOPA-induced dyskinesia.
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 naïve, 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 naïve animals significantly increased the potassium-evoked dopamine release. l-DOPA application also increased the dopamine peak amplitude in the dopamine-depleted l-DOPA naïve 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 naïve 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 naïve 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.
authors.affiliation: Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Nevalainen
authors.forename: Sara
authors.initials: S
authors.lastname: Af Bjerkén
authors.forename: Martin
authors.initials: M
authors.lastname: Lundblad
authors.forename: Greg A
authors.initials: GA
authors.lastname: Gerhardt
authors.forename: Ingrid
authors.initials: I
authors.lastname: Strömberg
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000473:pathology*; D004195:Disease Models, Animal; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000473:pathology* / Q000503:physiopathology; D004563:Electrochemistry / Q000379:methods; D005260:Female; D007839:Functional Laterality / Q000187:drug effects; D007980:Levodopa / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity; D011189:Potassium Chloride / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D012720:Severity of Illness Index; D013239:Stereotyped Behavior / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D007980:Levodopa; D011189:Potassium Chloride; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004296:Dopa Decarboxylase; D001058:Apomorphine; D004298:Dopamine