Electroacupuncture alleviated depression‐like behaviors in ventromedial prefrontal cortex of chronic unpredictable mild stress‐induced rats: Increasing synaptic transmission and phosphorylating dopamine transporter

Abstract

Aims Electroacupuncture (EA) shows advantages in both clinical practice and depression animal models. Dopaminergic‐related dysfunction in the prefrontal cortex (PFC) may be a hidden antidepressant mechanism of EA, where dopamine transporter (DAT) plays an essential role. This study aimed to investigate the synaptic transmission and DAT‐related changes of EA in depression. Methods Male Sprague–Dawley rats were subjected to 3‐week chronic unpredictable mild stress (CUMS). The successfully modeled rats were then randomly and equally assigned to CUMS, selective serotonin reuptake inhibitor (SSRI), and EA or SSRI + EA groups, followed by a 2‐week treatment respectively. After monitoring body weight and behavioral tests of all rats, the ventromedial PFC (vmPFC) tissue was collected for electrophysiology and the expression detection of DAT, phosphorylated DAT (p‐DAT), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and trace amine‐associated receptor 1 (TAAR1). Results Depressive‐like behaviors induced by CUMS were alleviated by EA, SSRI, and SSRI + EA treatments through behavioral tests. Compared with CUMS group, EA improved synaptic transmission in vmPFC by upregulating spontaneous excitatory postsynaptic currents amplitude. Molecularly, EA reversed the increased total DAT and p‐DAT expression as well as the decreased ratio of p‐DAT/total DAT along with the activation of TAAR1, cAMP, and PKA in vmPFC. Conclusion We speculated that the antidepressant effect of EA was associated with enhanced synaptic transmission in vmPFC, and the upregulated phosphorylation of DAT relevant to TAAR1, cAMP, and PKA may be the potential mechanism.

Treatment of Depression with Acupuncture Based on Pathophysiological Mechanism

“…Electroacupuncture (EA) may exert its antidepressant effects by regulating dopaminergic correlates in the PFC, with DAT playing a key role. 53 Behavioral tests 54 found that electroacupuncture treatment was able to alleviate depression-like behaviors triggered by chronic unpredictable mild stress (CUMS). EA improves neural function by enhancing synaptic transmission in the ventromedial prefrontal cortex (vmPFC) and upregulating spontaneous excitatory postsynaptic current amplitudes.…”