Chronic intermittent L-DOPA treatment induces changes in dopamine release
2009 (English)In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 108, no 4, 998-1008 p.Article in journal (Refereed) Published
3,4-Dihydroxyphenyl-l-alanine (l-DOPA)-induced dyskinesia often develops as a side effect of chronic l-DOPA therapy. This study was undertaken to investigate dopamine (DA) release upon l-DOPA treatment. Chronoamperometric measurements were performed in unilaterally DA-depleted rats, chronically treated with l-DOPA, resulting in dyskinetic and non-dyskinetic animals. Normal and lesioned l-DOPA naïve animals were used as controls. Potassium-evoked DA releases were significantly reduced in intact sides of animals undertaken chronic l-DOPA treatment, independent on dyskinetic behavior. Acute l-DOPA further attenuated the amplitude of the DA release in the control sides. In DA-depleted striata, no difference was found in potassium-evoked DA releases, and acute l-DOPA did not affect the amplitude. While immunoreactivity to serotonin uptake transporter was higher in lesioned striata of animals displaying dyskinetic behavior, no correlation could be documented between serotonin transporter-positive nerve fiber density and the amplitude of released DA. In conclusions, the amplitude of potassium-evoked DA release is attenuated in intact striatum after chronic intermittent l-DOPA treatment. No change in amplitude was found in DA-denervated sides of either dyskinetic or non-dyskinetic animals, while release kinetics were changed. This indicates the importance of studying DA release dynamics for the understanding of both beneficial and adverse effects of l-DOPA replacement therapy.
Place, publisher, year, edition, pages
2009. Vol. 108, no 4, 998-1008 p.
3, 4-dihydroxyphenyl-l-alanine, 3, 4-dihydroxyphenyl-l-alanine induced dyskinesia, 5-hydroxytryptamine or serotonin, chronoamperometry, dopamine, serotonin transporter
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:umu:diva-3140DOI: 10.1111/j.1471-4159.2008.05848.xPubMedID: 19196428OAI: oai:DiVA.org:umu-3140DiVA: diva2:141622