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

Brain Res. 2014 Jan 28:1544:33-44. doi: 10.1016/j.brainres.2013.11.028. Epub 2013 Dec 7.

Abstract

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.

Keywords: Acupuncture; FosB; GABA; Levodopa-induced dyskinesia; Parkinson's disease; l-dopa combination treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acupuncture Therapy*
  • Animals
  • Antiparkinson Agents / adverse effects*
  • Brain Chemistry*
  • Combined Modality Therapy
  • Glutamic Acid / analysis
  • Levodopa / adverse effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Movement / drug effects
  • Oxidopamine / toxicity
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / therapy*
  • Proto-Oncogene Proteins c-fos / drug effects
  • Proto-Oncogene Proteins c-fos / metabolism
  • Substantia Nigra / chemistry
  • gamma-Aminobutyric Acid / analysis

Substances

  • Antiparkinson Agents
  • Fosb protein, mouse
  • Proto-Oncogene Proteins c-fos
  • Glutamic Acid
  • Levodopa
  • gamma-Aminobutyric Acid
  • Oxidopamine