Electroacupuncture regulate hypothalamic-pituitary-adrenal axis and enhance hippocampal serotonin system in a rat model of depression

Neurosci Lett. 2016 Feb 26:615:66-71. doi: 10.1016/j.neulet.2016.01.004. Epub 2016 Jan 8.


Hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathogenesis of depression. Dysfunction of the hippocampal serotonin (5-hydroxytryptamine, 5-HT) system has been shown to be a key factor in depression. There is growing evidence that electro-acupuncture (EA) has antidepressant-like effect. However, the effect of EA on HPA axis and hippocampal serotonin system remains unknown. In our study, we investigated the antidepressant-like effect and mechanism of EA for depression rat models. Depression in rats was induced by chronic unpredictable mild stress (CUMS). EA treatment was administered once daily to CUMS rats for 14 days. The acupoints (ST36, bilateral and CV4) were selected. Untreated CUMS rats and normal rats were used as controls. Behavioral tests including forced swim test and open-field test were performed to evaluate the antidepressant effects of EA treatment. Hypothalamic corticotropin-releasing hormone (CRH) mRNA, plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were estimated as indices of HPA axis activity. Enzyme linked immunosorbent assay (ELISA) was performed to determine the concentrations of 5-HT in the hippocampus. Real-time PCR(RT-PCR)and Western blot were respectively used to detect the mRNA and protein levels of 5-hydroxytryptamine 1A receptor (5-HT1AR) in the hippocampus. Our results showed that EA treatment reversed the behavioral deficiency induced by CUMS in rats. EA treatment decreased CRH mRNA expression in the hypothalamic, and ACTH and CORT level in plasma, and markedly increased 5-HT concentration, 5-HT1AR (mRNA and protein) expression in the hippocampus. These results indicated that EA treatment could act on depression by modulating HPA axis and enhancing hippocampal 5-HT/5-HT1AR in CUMS Rats.

Keywords: 5-Hydroxytryptamine; 5-Hydroxytryptamine 1A receptor; Depression; Electro-acupuncture; Hippocampus; Hypothalamic–pituitary–adrenal axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / metabolism
  • Depression / metabolism
  • Depression / physiopathology
  • Depression / therapy*
  • Electroacupuncture*
  • Hippocampus / metabolism*
  • Hypothalamo-Hypophyseal System / physiology*
  • Male
  • Motor Activity
  • Pituitary-Adrenal System / physiology*
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Serotonin / metabolism*


  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone