Electroacupuncture ameliorates sleep deprivation-induced insomnia in mice by regulating the dopaminergic projections from VTA to NAc.

Abstract

BACKGROUND: The electroacupuncture (EA) has emerged as a potential therapeutic approach for the treatment of chronic insomnia, however, its underlying brain mechanism remain unclear. METHODS: Chronic sleep deprivation (CSD) mice models was established to investigate the effect of EA at acupoints of Yintang (EX-HN3), Shenmen (HT7), and Sanyinjiao (SP6) on CSD. With the methods of EEG/EMG recordings and chemogenetic manipulations, we explore the role of the dopaminergic projections from ventral tegmental area (VTA) to nucleus accumbens (NAc) in the therapeutic effects of EA on CSD-induced insomnia. RESULTS: We found that EA significantly alleviated CSD-induced insomnia, as indicated by an increased total sleep time and non-rapid eye movement (NREM) sleep during the dark period, along with attenuating the CSD-caused hyperactivity of VTA dopamine neurons in mice. Chemogenetic inhibition of the dopaminergic projections from VTA to NAc could restore the NREM sleep in CSD mice. Most importantly, the therapeutic effects of EA on CSD-induced insomnia was counteracted by activating the dopaminergic projections from VTA to NAc of mice. CONCLUSION: These findings suggested that the therapeutic effects of EA at EX-HN3, HT7 and SP6 are achieved by targeting the dopaminergic projections from VTA to NAc, which could be therapeutic approach for chronic insomnia.