Are cyclooxygenase-2 and nitric oxide involved in the dyskinesia of parkinson’s disease induced by L-DOPA?

Abstract

Inflammatory mechanisms are proposed to play a role in L-DOPA-induced dyskinesia. Cyclooxygenase-2 (COX2) contributes to inflammation pathways in the periphery and is constitutively expressed in the central nervous system. Considering that inhibition of nitric oxide (NO) formation attenuates L-DOPA-induced dyskinesia, this study aimed at investigating if aNOsynthase (NOS) inhibitor would change COX2 brain expression in animals with L-DOPA-induced dyskinesia. To this aim, male Wistar rats received unilateral 6-hydroxydopamine microinjection into the medial forebrain bundle were treated daily with L-DOPA (21 days) combinedwith 7-nitroindazole or vehicle. All hemi-Parkinsonian rats receiving L-DOPA showed dyskinesia. They also presented increased neuronal COX2 immunoreactivity in the dopaminedepleted dorsal striatum that was directly correlated with dyskinesia severity. Striatal COX2 co-localized with choline-acetyltransferase, calbindin and DARPP-32 (dopamine-cAMP-regulated phosphoprotein-32), neuronal markers of GABAergic neurons. NOS inhibition prevented L-DOPA-induced dyskinesia and COX2 increased expression in the dorsal striatum. These results suggest that increased COX2 expression after L-DOPA long-term treatment in Parkinsonian-like rats could contribute to the development of dyskinesia.