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Nitric Oxide and Cyclic Guanosine Monophosphate Signaling Mediates the Antidepressant Effects of Acupuncture in the Rat Model of Chronic Unpredictable Mild Stress

Wenya Huang, Xianjun Meng, Yang Huang, Siyu Liu, Anning Zhu, Peng Li, Yu Wang, Bangyi Tang, Jiahua Shi, Yiqing Cai

Department of Traditional Chinese Medicine Medical College, Xiamen University, Xiamen, Fujian, China (mainland)

Med Sci Monit 2019; 25:9112-9122

DOI: 10.12659/MSM.917593

Available online:

Published: 2019-11-30

BACKGROUND: Depression is a major mood disorder. Some patients have been reported to improve following acupuncture. This study aimed to investigate the effects of acupuncture on behaviors associated with depression in the chronic unpredictable mild stress (CUMS) rat model. The expression of signaling pathway components of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in the rat hippocampus and plasma were also measured.
MATERIAL AND METHODS: Male Sprague-Dawley rats (N=40) were divided into the control group (N=10), the model group (N=10), the acupuncture group (N=10), and the non-acupuncture group (N=10). The rat model was established by orphaning combined with chronic unpredictable mild stress (CUMS) for six weeks. The acupuncture group was given 21 days of treatment using acupoints (AP) or non-acupoints (NP). Rat behaviors associated with depression were tested using the sucrose preference test (SPT), the open field test (OFT), and the elevated plus maze (EPM) test. Enzyme-linked immunoassay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expression of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor subunits, NR1, NR2A, and NR2B in the rat plasma and hippocampus.
RESULTS: Acupuncture reversed the behaviors associated with depression in the CUMS rat model and reduced the expression of components of the NO and cGMP pathway in the rat hippocampus and plasma.
CONCLUSIONS: In the CUMS rat model, treatment with acupuncture reduced behaviors associated with depression, and these effects were associated with changes in the NO and cGMP signaling pathway.

Keywords: Acupuncture Therapy, Behavior and Behavior Mechanisms, Cyclic GMP-Dependent Protein Kinases, Depression, Nitric Oxide, Wnt Signaling Pathway