Acupuncture alleviates behavioral stereotypies of Tourette Syndrome via CB1 receptors in dopaminergic neurons of nigrostriatal system

Abstract Objective Tourette syndrome (TS) is a common neurological disorder characterized by behavioral stereotypies. Acupuncture has been found to improve stereotypical behavior in a clinical setting, but its mechanism remains unclear. The main pathogenesis of TS may result from the dysfunction of the dopamine (DA) system in the substantia nigra-striatal network. Moreover, endocannabinoids have therapeutic effects on TS by activating the CB1 receptors (CB1R). Methods In this study, we determined the optimal acupuncture treatment for TS. Further, we investigated whether CB1R could mediate the effects of acupuncture treatment on behavioral stereotypies of TS and regulate the concentration of DA in substantia nigra pars compacta (SNpc) and the dorsal striatum (dSTR). Results We found that both manual acupuncture and low-frequency electroacupuncture alleviated involuntary behavioral stereotypies in TS model mice, decreased the concentration of DA in the SNpc and dSTR, and increased CB1R expression in dopaminergic neurons in the SNpc. Targeted knockout of CB1R in dopaminergic neurons projecting from SNpc to dSTR reversed the effects of acupuncture. Conclusion Our results support that CB1R in dopaminergic neurons projecting from SNpc to dSTR is involved in acupuncture treatment to alleviate stereotypical behavior in TS model mice.