Aspirin attenuates L-DOPA-induced dyskinesia in hemi-parkinsonian rats

Background: At present, L-DOPA remained the gold standard therapy for motor symptoms of Parkinson’s disease (PD) patients. However, prolonged administration of L-DOPA led to the development of dyskinesia. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), had been widely used to relieve pain and inflammation. Recent studies indicated aspirin produced neuroprotection against dopamine (DA) neuronal loss in animal model. This study aimed to explore the effects of aspirin pre-treatment and co-treatment with L-DOPA on DA neurotoxicity and L-DOPA-induced dyskinesia (LID) as well.Methods: Rats received a single 6-hydroxydopamine (6-OHDA) injection into substantia nigra to induce DA neuronal loss. For aspirin pre-treatment before L-DOPA studies: One day after 6-OHDA stimulation, rats were daily administrated with aspirin for 3 weeks followed by daily L-DOPA treatment along with aspirin for additional 3 weeks. For aspirin co-treatment with L-DOPA studies: Three weeks after 6-OHDA administration, rats were daily treated by L-DOPA together with aspirin for another 3 weeks. DA neurotoxicity was analyzed via rat PD-like behavior test and DA neuronal counting. The movement disorders of dyskinesia triggered by L-DOPA were determined by the abnormal involuntary movements (AIM) scores analysis.Results: we demonstrated both aspirin pre-treatment and co-treatment exerted anti-LID effects during L-DOPA treatment on 6-OHDA-lesioned rats. In addition, aspirin not only ameliorated DA neuronal damage, but also reduced the development of dyskinesia without affecting L-DOPA efficacy. Furtherly, inhibition of glial cells activation and the subsequent neuroinflammatory response might be involved in aspirin-attenuated dyskinesia.Conclusion: the present study suggested aspirin could have beneficial potential to attenuate LID in PD.