Mass spectrometry imaging identifies abnormally elevated brain <scp>l</scp> -DOPA levels and extrastriatal monoaminergic dysregulation in <scp>l</scp> -DOPA–induced dyskinesia
Elva Fridjonsdottir, Mohammadreza Shariatgorji, Anna Nilsson, Theodosia Vallianatou, Luke R. Odell, Luke S. Schembri, Per Svenningsson, Pierre‐Olivier Fernagut, A.R. Crossman, Erwan Bézard, Per E. Andrén
Abstract
-methyldopa, in all measured brain regions of dyskinetic animals and increases in dopamine and metabolites in all regions analyzed except the striatum. In dyskinesia, dopamine levels correlated well with l-DOPA levels in extrastriatal regions, such as hippocampus, amygdala, bed nucleus of the stria terminalis, and cortical areas, but not in the striatum. Our results demonstrate that l-DOPA-induced dyskinesia is linked to a dysregulation of l-DOPA metabolism throughout the brain. The inability of extrastriatal brain areas to regulate the formation of dopamine during l-DOPA treatment introduces the potential of dopamine or even l-DOPA itself to modulate neuronal signaling widely across the brain, resulting in unwanted side effects.