RT Journal Article SR Electronic T1 Electro-acupuncture Alleviates METH Withdrawal-induced Spatial Memory Deficits by Restoring Astrocyte-drived Glutamate Uptake in dCA1 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.05.20.106153 DO 10.1101/2020.05.20.106153 A1 Pengbo Shi A1 Zhaosu Li A1 Xing Xu A1 Jiaxun Nie A1 Dekang Liu A1 Qinglong Cai A1 Yonghua Zhao A1 Yun Guan A1 Feifei Ge A1 Xiaowei Guan YR 2020 UL http://biorxiv.org/content/early/2020/05/26/2020.05.20.106153.abstract AB Methamphetamine (METH) is frequently abused drug and produces cognitive deficits. METH could induce hyper-glutamatergic state in the brain, which could partially explain METH-related cognitive deficits, but the synaptic etiology remains incompletely understood. To address this issue, we explored the role of dCA1 tripartite synapses and the potential therapeutic effects of electro-acupuncture (EA) in the development of METH withdrawal-induced spatial memory deficits in mice. We found that METH withdrawal weakened astrocytic capacity of glutamate (Glu) uptake, but failed to change Glu release from dCA3, which lead to hyper-glutamatergic excitotoxicity at dCA1 tripartite synapses. By restoring the astrocytic capacity of Glu uptake, EA treatments suppressed the hyper-glutamatergic state and normalized the excitability of postsynaptic neuron in dCA1, finally alleviated spatial memory deficits in METH withdrawal mice. These findings indicate that astrocyte at tripartite synapses might be a key target for developing therapeutic interventions against METH-associated cognitive disorders, and EA represent a promising non-invasive therapeutic strategy for the management of drugs-caused neurotoxicity.Competing Interest StatementThe authors have declared no competing interest.