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Chronic intermittent L ‐DOPA treatment induces changes in dopamine release
Author(s) -
Lundblad Martin,
Af Bjerkén Sara,
Cenci M. Angela,
Pomerleau Francois,
Gerhardt Greg A.,
Strömberg Ingrid
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05848.x
Subject(s) - dopamine , dyskinesia , striatum , serotonin , levodopa , dihydroxyphenylalanine , medicine , chemistry , endocrinology , potassium , pharmacology , anesthesia , parkinson's disease , receptor , disease , organic chemistry
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.