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. 2021 Aug 27;15:698967. doi: 10.3389/fnins.2021.698967

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Copyright © 2021 Wang, Qin, Wang, Yang, Liu, Li, Jiang, Lu, Wang and Lu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Proposed mechanisms of action by which EA ameliorated morphine-induced tolerance in mice. Chronic morphine increased the levels of cAMP, and the levels of phosphorylation levels of protein kinase A (PKA), extracellular regulated protein kinases (ERK) and cAMP response element-binding (CREB) in morphine-induced tolerance. After the treatment of Electro-Acupuncture, the increased of cAMP, p-PKA C, p-ERK, and p-CREB were significantly decreased in morphine-induce tolerance. Simultaneously, RNA sequencing reval the underlying molecular targets of EA treatment on morphine-induced tolerance maybe KO04080 (Neuroactive ligand-receptor interaction) and KO04668 (TNF signaling pathway).