Tracking Gastrointestinal Transit of Solids in Aged Rats as Pharmacological Models of Chronic Dysmotility

Background: Dysmotility in the gastrointestinal tract (GI) 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. Methods: Male rats (18 months) were given 0, 1, 2, or 4 mg/kg/day prucalopride or loperamide (in DMSO) for seven days by continuous 7 day dosing. To determine the GI region-specific effect, transit of 6 metallic beads was tracked over 12 hours 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 post-mortem. Key Results: Loperamide (1 mg/kg) slowed stomach emptying and GI transit at 9 and 12 hours. 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 hours compared to controls. Conclusions & Inferences: We reveal 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 colonic transit.