Coordinated and spatial upregulation of arc in striatonigral neurons correlates with L-dopa-induced behavioral sensitization in dyskinetic rats.

Abstract Although oral administration of L-Dopa remains the best therapyfor Parkinson disease, its long-term administration causes the appear-ance of abnormal involuntary movements such as dyskinesia. Althoughpersistent striatal induction of some genes has already been asso-ciated with such pathologic profiles in hemiparkinsonian rats, molec-ular and cellular mechanisms underlying such long-term adaptationsremain to be elucidated. In this study, using a rat model of L-Dopa-induceddyskinesia, we report that activityregulated cytoskeletal (Arc)-associated protein is strongly upregulated in the lesioned striatum andthat the extent of its induction further varies according to theoccurrence or absence of locomotor sensitization. Moreover, Arc ispreferentially induced, along with FosB, nur77, and homer-1a, instriatonigral neurons, which express mRNA encoding the precursorof dynorphin. Given the likely importance of Arc in the regulation ofcytoskeleton during synaptic plasticity, its upregulation supports thehypothesis that a relationship exists between cytoskeletal modifica-tions and the longlasting action of chronically administrated L-Dopa.Key Words: Arc, Dynorphin, Dyskinesia, homer-1a, L-Dopa,Locomotor sensitization, nur77.