Involvement of Hippocampal AMPA Receptors in Electroacupuncture Attenuating Depressive-Like Behaviors and Regulating Synaptic Proteins in Rats Subjected to Chronic Unpredictable Mild Stress

A large body of evidence has suggested that the disruptions of neural plasticity in the brain play a pivotal role in major depressive disorder (MDD). Electroacupuncture (EA) therapy has been shown to be an effective treatment modality for MDD. However, the mechanism underling the antidepressive effect of EA treatment has not been clearly elucidated. This study aimed to investigate the antidepressant-like effects of EA associated with its protection effect of synaptic structural plasticity. An MDD model was induced by exposing Sprague Dawley rats to chronic unpredictable mild stress (CUMS). EA stimulation (Hegu and Taichong) and AMPA receptor (AMPAR) antagonist NBQX intrahippocampal injection were used to treat the depressed rats. We found EA improved behavioral performance, enhanced synaptic structural plasticity, and upregulated gene and protein levels of GluR1, GluR2, Stargazin, Pick1, SYP, PSD-95, and GAP-43. AMPAR antagonist NBQX had the opposite effect on behavioral performance, synaptic plasticity, and the aforementioned genes and proteins. These results suggest that EA has a potent antidepressant effect, likely through upregulated expression of the AMPAR and protected neural plasticity in CUMS-treated rats.