Chronic intermittent L-DOPA treatment induces changes in dopamine release

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.