Mechanisms of Electroacupuncture in Alleviating Stress-induced Irritable Bowel Syndrome in Rats: The Role of the Central Amygdala

Abstract

Abstract Visceral hypersensitivity (VH) and anxiety are the main characteristics of irritable bowel syndrome (IBS) patients. Acupuncture has been demonstrated to be effective as a non-pharmacological approach for treating IBS. The central amygdala (CeA) is a key brain nucleus closely related to mediate integration of abdominal pain, gastrointestinal motility and anxiety. In the present study, we investigated whether and how the CeA mediate the protective effects of electroacupuncture (EA) against VH and anxiety in water avoidance stress (WAS)-induced IBS rats. Visceral sensitivity was assessed via abdominal withdrawal reflex and diarrhea index. Anxiety-related behavior was measured via open field test. The expression of c-Fos, GAD65, SYN1, PSD95 and BDNF in CeA were measured by using immunofluorescence or western blot. The chemogenetic method was used to activate or inhibit the selected target neurons. We found that EA attenuated WAS-induced gastrointestinal symptoms and anxiety-like behaviors with reduced expression of c-Fos, GAD65, SYN1, PSD95 and BDNF in the CeA. WAS-induced dysfunction was alleviated by inhibiting CeA neurons and the effects of EA treatment were counteracted by activating CeA neurons. Moreover, activating and inhibiting gamma-aminobutyric acidergic (GABAergic) neurons in the CeA can impede and enhance the effects of EA treatment, respectively. These data suggest that EA is effective to ameliorate stress-induced VH and anxiety via alleviating neuronal hyperactivity in the CeA, particularly targeting the hyperactivity of GABAergic neurons in the CeA, and suppressing enhanced synaptic plasticity in this region.