Acupuncture Alleviates Anxiety and 22-kHz Ultrasonic Vocalizations in Rats Subjected to Repeated Alcohol Administration by Modulating the Brain-Derived Neurotrophic Factor/Corticotropin-Releasing Hormone Signaling Pathway

Int J Mol Sci. 2021 Apr 14;22(8):4037. doi: 10.3390/ijms22084037.


The Shenmen point (acupuncture point heart 7: HT7), located in the heart meridian, is frequently used to treat mental disorders, including drug addiction, anxiety, and depression. This study aimed to determine how HT7 regulates anxiety and negative emotions caused by repeated alcohol administration, focusing on the amygdala and paraventricular nucleus (PVN). Repeated administration of alcohol (ETOH; 2 g/kg, i.p. injection, 16% v/v) for 14 days increased the corticosterone (CORT) levels, and HT7 stimulation reduced the plasma CORT levels. HT7 stimulation mitigated anxiety-like behaviors and reduced 22-kHz ultrasonic vocalizations in rats receiving repeated ETOH injections. HT7 stimulation increased the amygdala expression of mature brain-derived neurotropic factor (mBDNF) and phosphorylated tropomyosin receptor kinase B (pTrkB) and decreased the PVN corticotropin-releasing hormone (CRH) expression. Amygdala microinjections of the TrkB antagonist ANA-12 (0.1 pmol/1 μL) reversed the increase in PVN CRH levels. The reduced PVN CRH levels were regulated by CRH-expressing neurons in the amygdala, and the increased amygdala CRH levels were affected by the HT7-stimulation induced increases in mBDNF. HT7 stimulation alleviates increased stress hormone levels and mitigates anxiety and negative emotions caused by repeated ETOH administration. These results provide scientific support for the clinical use of acupuncture to treat various alcoholism-induced diseases.

Keywords: BDNF; CRH; USVs; acupuncture; alcohol.

MeSH terms

  • Acupuncture Points
  • Acupuncture Therapy*
  • Amygdala / metabolism
  • Animals
  • Anxiety / blood
  • Anxiety / physiopathology*
  • Behavior, Animal
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / metabolism*
  • Elevated Plus Maze Test
  • Ethanol / administration & dosage*
  • Ethanol / blood
  • Male
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Phosphorylation
  • Rats
  • Rats, Wistar
  • Receptor, trkB / metabolism
  • Signal Transduction*
  • Ultrasonics*
  • Vocalization, Animal*


  • Brain-Derived Neurotrophic Factor
  • Ethanol
  • Corticotropin-Releasing Hormone
  • Receptor, trkB
  • Corticosterone