期刊
JOURNAL OF NEUROCHEMISTRY
卷 118, 期 1, 页码 12-23出版社
WILEY
DOI: 10.1111/j.1471-4159.2011.07292.x
关键词
5-HT; chronoamperometry; L-DOPA-induced dyskinesia; SERT
资金
- Swedish Research Council [09917]
- Umea University Medical Faculty
- Konung Gustav V och Drottning Victoria's fund, Sweden
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 naive, 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 naive animals significantly increased the potassium-evoked dopamine release. L-DOPA application also increased the dopamine peak amplitude in the dopamine-depleted L-DOPA naive 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 naive 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 naive 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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