Dopaminergic signaling in prefrontal cortex contributes to the antidepressant effect of electroacupuncture: An iTRAQ-based proteomics analysis in a rat model of CUMS(sic)(sic)(sic)

Electroacupuncture (EA) is used as an adjunctive treatment for depression. This study was conducted to evaluate the efficacy and mechanisms of EA in the depressive rat model induced by chronic unpredictable mild stress (CUMS) in male adult Wistar rats. The underlying mechanisms were explored by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of the proteins in the prefrontal cortex (PFC), and observing the number of the PFC neurons stained with hematoxylin and eosin (H&E) and synaptic morphological changes under transmission electron microscopy (TEM). The results showed that EA plus paroxetine (EA + Par) for 1 week significantly relieved depression-like anhedonia symptoms and improved anxiety-like behavior, accompanied by the improvements in synaptic morphology and a significant increase of PFC neurons. Moreover, EA or paroxetine alone significantly alleviated anhedonia symptoms after 2 weeks of intervention. Additionally, iTRAQ analysis showed that dopaminergic signaling was significantly altered in CUMS rats after 1 week of EA treatment. As the critical enzyme of this pathway, aromatic-l-amino-acid decarboxylase (DDC) was significantly upregulated after the treatment with EA + Par for 1 week. These findings suggested that the dopaminergic signaling pathway in PFC may be involved in the antidepressant mechanisms of EA.