Combined treatment with acupuncture reduces effective dose and alleviates adverse effect of l-dopa by normalizing Parkinson's disease-induced neurochemical imbalance

• We first reported the effect of combined treatment of l-dopa with acupuncture.
• This treatment reduced the optimal dose of l-dopa for improving motor dysfunction.
• Combined treatment alleviated l-dopa-induced dyskinetic motor symptoms.
• Abnormal increase of striatal FosB activation was alleviated by the treatment.
• GABA/glutamate assay showed normalisation of imbalance within the basal ganglia.

This study first showed the behavioural benefits of novel combination therapy of l-dopa with acupuncture on Parkinson's disease, and its underlying mechanisms within basal ganglia. The previous study reported that acupuncture may improve the motor function of a Parkinson's disease (PD) mouse model by increasing the dopamine efflux and turnover ratio of dopamine. Hence, we hypothesised that combining l-dopa with acupuncture would have a behavioural benefit for those with PD. We performed unilateral injections of 6-OHDA into the striatum of C57Bl/6 mice to model hemi-Parkinsonian attributes. To test motor function and dyskinetic anomalies, we examined cylinder behaviour and abnormal involuntary movement (AIM), respectively. We found that (1) a 50% reduced dose of l-dopa (7.5 mg/kg) combined with acupuncture showed an improvement in motor function that was comparable to mice given the standard dose of l-dopa treatment (15 mg/kg) only, and that (2) the combination treatment (l-dopa +acupuncture) was significantly superior in reducing AIM scores when equivalent doses of l-dopa were used. The combination treatment also significantly reduces the abnormal increase of GABA contents in the substantia nigra compared to the standard l-dopa treatment. Furthermore, abnormal expression of FosB, the immediate early gene of l-dopa induced dyskinesia (LID), was mitigated in the striatum by the combination treatment. All of these results indicate that acupuncture enhances the benefits of l-dopa on motor function with reduced dose of l-dopa and alleviating LID by normalising neurochemical imbalance within the basal ganglia.