Background: Converging evidence indicates that the glutamatergic system and glia are
directly implicated in the pathophysiology of depression. Clinical studies indicate that
electroacupuncture (EA) has anti-depressant-like effects with low side effects for depression.
However, the underlying antidepressant mechanism of acupuncture remains obscure.
Methods: Chronic unpredictable mild stress (CUMS)-induced depressive rats were used to induce
depressive-like behavior and evaluated by the weight change, open field test, sucrose preference
test, and novelty suppressed feeding test. EA, NMDA receptor subunit 2A antagonist (NR2A RA)
or NMDA receptor subunit 2B antagonist (NR2B RA) was used for comparison. Highperformance
liquid chromatography (HPLC) was performed to detect the content of hippocampal
glutamate, while western blot was performed for the hippocampal protein expression levels of
calcium/calmodulin-dependent protein kinase II (CaMKII), Bax, caspase 3 and B-cell lymphoma-2
(Bcl-2). The distribution of glutamate ionotropic receptor NMDA type subunit 2A (NR2A),
neuronal nuclear protein (NeuN), glutamate ionotropic receptor NMDA type subunit 2B (NR2B),
and glial fibrillary acidic protein (GFAP) were detected by immunofluorescence.
Results: Significant depression behavior (reduced body weight and sucrose preference, increased
feeding and immobility time) was produced in CUMS-induced depressive rats, which was reversed
significantly by EA. EA decreased hippocampal glutamate level. EA led to a significant decrease
in expression levels of Bax, caspase 3, and CaMK II accompanied by increased Bcl-2 expression
levels. Furthermore, EA significantly increased NR2A expression level as well as decreased NR2B
expression level in the hippocampus.
Conclusion: EA ameliorated depression-like behavior in CUMS rats, which might be mediated, at
least in part, by regulating the glutamate, NMDA receptors, and apoptosis in the hippocampus.