title: Early-life stress selectively affects gastrointestinal but not behavioral responses in a genetic model of brain-gut axis dysfunction.
abstract: BACKGROUND
  Early-life stress and a genetic predisposition to display an anxiety- and depressive-like phenotype are associated with behavioral and gastrointestinal (GI) dysfunction. Animals exposed to early-life stress, and those genetically predisposed to display anxiety or depressive behaviors, have proven useful tools in which to study stress-related GI disorders, such as irritable bowel syndrome (IBS). IBS is a heterogeneous disorder, and likely a consequence of both genetic and environmental factors. However, the combined effects of early-life stress and a genetic predisposition to display anxiety- and depression-like behaviors on GI function have not been investigated.
  
  
  METHODS
  We assessed the effect of maternal separation (MS) on behavioral and GI responses in WKY animals relative to a normo-anxious reference strain.
  
  
  RESULTS
  Both non-separated (NS) WKY and WKY-MS animals displayed anxiety-like responses in the open-field test and depressive-like behaviors in the forced swim test relative to Sprague-Dawley rats. However, MS had no further influence on anxiety- and depressive-like behaviors exhibited by this stress-prone rat strain. Similarly, corticosterone levels measured after the OFT were insensitive to MS in WKY animals. However, WKY-MS displayed significantly increased colonic visceral hypersensitivity, fecal output, and altered colonic cholinergic sensitivity.
  
  
  CONCLUSIONS
  Our data suggest that early-life stress, on the background of a genetic predisposition to display an anxiety- and depressive-like phenotype, selectively influences GI function rather than stress-related behaviors. Thus, our findings highlight the importance of genetic predisposition on the outcome of early-life adversity on GI function.
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland.
authors.forename: N P
authors.initials: NP
authors.lastname: Hyland
authors.forename: S M
authors.initials: SM
authors.lastname: O'Mahony
authors.forename: D
authors.initials: D
authors.lastname: O'Malley
authors.forename: C M
authors.initials: CM
authors.lastname: O'Mahony
authors.forename: T G
authors.initials: TG
authors.lastname: Dinan
authors.forename: J F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology; D003106:Colon / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005769:Gastrointestinal Motility; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000503:physiopathology*; D017136:Ion Transport; D008297:Male; D008426:Maternal Deprivation; D010147:Pain Measurement; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology*
chemical_list: D003345:Corticosterone
keywords: Wistar Kyoto; colon; gene-environment; maternal separation; visceral hypersensitivity