title: Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility.
abstract: Dysmotility in the gastrointestinal (GI) tract often leads to impaired transit of luminal contents leading to symptoms of diarrhea or constipation. The aim of this research was to develop a technique using high resolution X-ray imaging to study pharmacologically induced aged rat models of chronic GI dysmotility that mimic accelerated transit (diarrhea) or constipation. The 5-hydroxytryptamine type 4 (5-HT4 ) receptor agonist prucalopride was used to accelerate transit, and the opioid agonist loperamide was used to delay transit.
  
  
  
  Male rats (18 months) were given 0, 1, 2, or 4 mg/kg/day prucalopride or loperamide (in dimethyl sulfoxide, DMSO) for 7 days by continuous 7-day dosing. To determine the GI region-specific effect, transit of six metallic beads was tracked over 12 h using high resolution X-ray imaging. An established rating scale was used to classify GI bead location in vivo and the distance beads had propagated from the caecum was confirmed postmortem.
  
  
  
  Loperamide (1 mg/kg) slowed stomach emptying and GI transit at 9 and 12 h. Prucalopride (4 mg/kg) did not significantly alter GI transit scores, but at a dose of 4 mg/kg beads had moved significantly more distal than the caecum in 12 h compared to controls.
  
  
  
  We report a novel high-resolution, non-invasive, X-ray imaging technique that provides new insights into GI transit rates in live rats. The results demonstrate that loperamide slowed overall transit in aged rats, while prucalopride increased stomach emptying and accelerates colonic transit.
authors.affiliation: Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch, Palmerston North, New Zealand.
authors.forename: J E
authors.initials: JE
authors.lastname: Dalziel
authors.affiliation: Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch, Palmerston North, New Zealand.
authors.forename: W
authors.initials: W
authors.lastname: Young
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Bercik
authors.affiliation: School of Medicine, Flinders University, Adelaide, SA, Australia.
authors.forename: N J
authors.initials: NJ
authors.lastname: Spencer
authors.affiliation: Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch, Palmerston North, New Zealand.
authors.forename: L J
authors.initials: LJ
authors.lastname: Ryan
authors.affiliation: Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch, Palmerston North, New Zealand.
authors.forename: K E
authors.initials: KE
authors.lastname: Dunstan
authors.affiliation: Bioinformatics Mathematics and Statistics, AgResearch, Palmerston North, New Zealand.
authors.forename: C M
authors.initials: CM
authors.lastname: Lloyd-West
authors.affiliation: Fonterra Co-operative Group, Palmerston North, New Zealand.
authors.forename: P K
authors.initials: PK
authors.lastname: Gopal
authors.affiliation: Fonterra Co-operative Group, Palmerston North, New Zealand.
authors.forename: N W
authors.initials: NW
authors.lastname: Haggarty
authors.affiliation: Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch, Palmerston North, New Zealand.|Riddet Institute, Massey University, Palmerston North, New Zealand.|Gravida: National Centre for Growth and Development, The University of Auckland, Auckland, New Zealand.
authors.forename: N C
authors.initials: NC
authors.lastname: Roy
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D003106:Colon / Q000187:drug effects*; D004063:Digestion / Q000187:drug effects; D004195:Disease Models, Animal; D005746:Gastric Emptying / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005767:Gastrointestinal Diseases; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D008139:Loperamide / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001572:Benzofurans; D005765:Gastrointestinal Agents; C406662:prucalopride; D008139:Loperamide
keywords: colon transit; constipation; gastrointestinal transit; loperamide; prucalopride