CONICET | Buscador de Institutos y Recursos Humanos

L-dopa-induced dyskinesia (LID) remains as amajor problem in the treatment of Parkinson's disease. Because striatalinterneurons play an important role in regulating striatal network function, weanalyzed changes in number and activity of the different interneuronpopulations following 6-hydroxydopamine (6-OHDA) DA-depletion and acute orchronic treatment with a dyskinesia-inducing dose of L-DOPA. C57BL6/J mice were injected with 6-OHDA or vehicle in the medial forebrainbundle and treated with L-DOPA or saline, for 1 or 18 days. LID andforelimb asymmetry were assessed every 4 days. We studied changes in number byimmunohistochemistry for interneuronal markers and tyrosine hydroxylase. Parvalbumin-containing interneurons density was reduced after DA-depletionregardless of the treatment regimen. Calretinin-containing interneurons densitywas increased in 6-OHDA mice but not after L-DOPA treatment. Cholinergic andsomatostatin-containing interneurons did not change under any condition. Interneuronal activity was evaluated by co-immunofluorescence with c-Fos.6-OHDA lesion induced c-Fos expression which was further increased after anacute dose of L-DOPA and markedly increased after chronic treatment. By meansof double-immunolabeling, we determined that 47% of the somatostatin-containingand 7% of the cholinergic interneurons expressed c-Fos, suggesting anoveractivity of these populations, possibly involved in striatal dysfunction.Striatal TH-immunoreactive cells were only found in L-DOPA-chronically treatedmice. They showed full c-Fos co-localization but did not express any of theinterneuronal markers. Our findings suggest that changes in striatalinterneurons contribute to the maladaptive state after DA-depletion. Chronictreatment with L-DOPA fails to reestablish the basal physiological landscapeand induces additional changes in striatal microcircuitry.