19-06-08(15:14:24)
Authors:
Strömberg I, 1
af Bjerkén S, 1
Nevalaine N, 1
Gerhardt G, 2
Institutions:
1, Integrative Medical Biology, Umeå University, Umeå, Sweden
2, Anatomy, Neurobiology, Neurology, University of Kentucky Med Ctr, Lexington, KY, USA
Title of abstract : L-DOPA CONVERSION TO DOPAMINE IN THE RAT DOPAMINE-DEPLETED STRIATUM
Abstract text:
L-DOPA therapy is a routinely used and efficient treatment of the symptoms of Parkinson’s disease. However, with chronic exposure, side effects such as L-DOPA induced dyskinesia often evolve. The cause of L-DOPA induced dyskinesia is still unknown; fluctuations in dopamine release resulting in uneven transmitter distribution are though a possible explanation. Moreover, L-DOPA conversion to dopamine has been suggested to occur in serotonergic nerve fiber terminals in dopamine-depleted striata. This study investigates the conversion of L-DOPA to dopamine in rat striata using in vivo chronoamperometry. Potassium-stimulated dopamine release was monitored in the striatum before and after local L-DOPA application. Recordings were performed in intact and 6-OHDA-lesioned as well as in normal striatum. It was demonstrated that locally applied L-DOPA can be uptaken and later released as dopamine upon potassium-stimulation in the dopamine-depleted striatum, suggesting conversion in non-dopaminergic nerve fibers. In normal and intact hemisphere of 6-OHDA lesioned animals, local L-DOPA administration significantly increased the peak amplitudes of released dopamine. Interestingly, the peak amplitudes were higher in the intact side of unilaterally lesioned animals compared to normal striatum, after L-DOPA application. Antibodies visualizing the serotonin transporter (SERT) demonstrated no differences in striatal nerve fiber density between normal, intact or 6-OHDA-depleted striata. Furthermore, this study demonstrated an alternate route of L-DOPA conversion to dopamine, where L-DOPA application resulted in an immediate dopamine signal. This might suggest a non-neuronal conversion of L-DOPA to dopamine. In conclusion, L-DOPA can be converted to dopamine in dopamine-depleted striatum and be released as dopamine upon potassium-stimulation.
