Acupuncture has increasingly been used as an alternative therapy for treatment of Parkinson's disease (PD). However, the efficacy of acupunture for PD still remains unclear. The present study was designed to objectively and safely monitor anti-parkinsonian effects of electroacupuncture (EA) and brain activity in nonhuman primates modeling human PD. Six middle-aged rhesus monkeys were extensively studied by a computerized behavioral testing battery and by pharmacological MRI (phMRI) scans with specific dopaminergic drug stimulations. All animals were evaluated for behavior and phMRI responses under normal, parkinsonian, parkinsonian with EA treatment and parkinsonian after EA treatment conditions. Stable parkinsonian features were observed in all animals prior to entering the EA study and positive responses to levodopa (L-dopa) challenge were also seen in all animals. The results demonstrated that chronic EA treatments could significantly improve the movement speed and the fine motor performance time during the period of EA treatments, and the effectiveness of EA could be detected even 3 months after the EA treatment. The phMRI data revealed that chronic EA treatments could alter neuronal activity in the striatum, primary motor cortex (M1), cingulate gyrus and global pallidus externa (GPe) in the ipsilateral hemisphere to MPTP lesions. As seen in the changes of parkinsonian features, the residual effects of phMRI responses to apomorphine (APO) challenge could also be found in the aforementioned areas. The results strongly suggest that anti-parkinsonian effects of EA can be objectively assessed, and the method used in the present study could be translated into the human clinic with some minor modifications.

The results from this proof-of-concept study support the utility of our repeated intranasal dosing methodology in awake Rhesus macaques, to evaluate the effects of neuroactive compounds on the NHP brain. Additionally, results indicate that DNSP-11 can be safely and effectively delivered intranasally in MPTP-treated NHPs, while engaging the DA system.