Environmental enrichment prevents chronic stress-induced brain-gut axis dysfunction through a GR-mediated mechanism in the central nucleus of the amygdala.

Abstract

Cognitive behavioral therapy (CBT) improves quality of life of patients with irritable bowel syndrome (IBS), a disorder characterized by chronic visceral pain and abnormal bowel habits. Whether CBT can actually improve visceral pain in IBS patients is still unknown. The aim of this study is to evaluate whether environment enrichment (EE), the animal analog of CBT, can prevent stress-induced viscero-somatic hypersensitivity through changes in glucocorticoid receptor (GR) signaling within the central nucleus of the amygdala (CeA). Rats were housed in either standard housing (SH) or EE for 7days before and during daily water avoidance stress (WAS) exposure (1-h/d for 7days). In the first cohort, visceral and somatic sensitivity were assessed via visceromotor response to colorectal distention and von Frey Anesthesiometer 24hous and 21days after WAS. In another cohort, the CeA was isolated for GR mRNA quantification. Environment enrichment for 7days before and during the 7days of WAS persistently attenuated visceral and somatic hypersensitivity when compared to rats placed in SH. Environment enrichment exposure also prevented the WAS-induced decrease in GR expression in the CeA. Pre-exposure to short-term EE prevents the stress-induced downregulation of GR, and inhibits visceral and somatic hypersensitivity induced by chronic stress. These results suggest that a positive environment can ameliorate stress-induced pathology and provide a non-pharmacological therapeutic option for disorders such as IBS.