Intrastriatal inhibition of aromatic amino acid decarboxylase prevents L-DOPA-induced dyskinesia: A bilateral reverse in vivo microdialysis study in 6-hydroxydopamine lesioned rats

L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia consists of involuntary choreiform and dystonic movements. Here we report whether intrastriatal L-DOPA itself is able to trigger dyskinetic behavior and which role the neurotransmitter dopamine (DA) and its metabolites play. Intrastriatal L-DOPA as well as DA administration at the 6-hydroxydopamine (6-OHDA) lesioned side led to a significant appearance of dyskinetic behavior, whereas DA metabolites were ineffective. Intrastriatal inhibition of the enzyme aromatic amino acid decarboxylase (AADC) by benserazide prevented the appearance of L-DOPA-induced dyskinetic movements at the lesioned side. Principle component analysis of DA and DA metabolite levels with dyskinesia scores after L-DOPA/benserazide (6/15 mg/kg) administration indicated a significant correlation only for DA, whereas DA metabolites did not show any significant correlation with the occurrence of dyskinetic behavior. We conclude that intrastriatal L-DOPA itself is not able to induce dyskinetic movements, whereas the increase of intrastriatal DA levels is instrumental for L-DOPA- and DA-induced dyskinetic behavior. (C) 2007 Elsevier Inc. All rights reserved.