title: Altered physiology of acid secretion in depression-prone Flinders rats results in exacerbated NSAID and stress-induced gastric damage.
abstract: BACKGROUND
  Flinders Sensitive Line (FSL) rats are characterized by hypersensitivity to cholinergic stimuli and have been extensively used for studying depressive disorders. A link between depression and peptic ulcers has long been established; however, there is a lack of data from animal models.
  
  
  METHODS
  We studied the physiology of acid secretion in FSL and Flinders Resistant Line (FRL) rats in vivo and in vitro. We also examined the susceptibility of Flinders rats to water immersion restraint stress (WIRS) or NSAID-induced gastric damage and explored the effect of an anticholinergic agent, atropine, in reversing this effect.
  
  
  RESULTS
  Basal acid output was more than twofold greater in FSL compared with FRL rats in vivo, 213.5 and 92.8 μEq/3 h/100 g (P = 0.02), respectively. Carbachol was a more potent secretagog in vitro, and somatostatin was a less potent inhibitory agent, while paradoxically stimulating acid secretion over and above the carbachol response in gastric glands from FSL rats. The FSL rats were more susceptible to indomethacin and WIRS-induced gastric mucosal damage compared with FRL rats. Atropine reduced acid output, which resulted in a reduction in indomethacin and stress-induced gastric damage in FSL rats.
  
  
  CONCLUSIONS
  Our study, for the first time, demonstrates that the altered vagally mediated physiology of acid secretion in depression-prone FSL rats contributes to gastric hypersecretion and, consequently, results in exacerbated stress and NSAID-induced gastric damage. Flinders rats may be a useful animal model for studying acid-related and also gastrointestinal functional disorders in depression.
authors.affiliation: Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: I T
authors.initials: IT
authors.lastname: Padol
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: R H
authors.initials: RH
authors.lastname: Hunt
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D051381:Rats; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018727:Muscarinic Antagonists; D001285:Atropine