AbstractMethamphetamine (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 unclear. Here, we investigated the role of dCA1 tripartite synapses and the potential therapeutic effects of electro-acupuncture (EA) in the METH withdrawal-induced spatial memory deficits. METH withdrawal weakened astrocytic capacity of Glu uptake, but

more »

... ailed to change Glu release from dCA3, resulting in 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 novel 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.