Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility

J Dalziel, W Young, Premysl Bercik, Nicholas Spencer, L Ryan, K Dunstan, C Lloyd-West, P Gopal, N Haggarty, N Roy

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    19 Citations (Scopus)

    Abstract

    Background: 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. Methods: 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. Key Results: 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. Conclusions & Inferences: 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.

    Original languageEnglish
    Pages (from-to)1241-1251
    Number of pages11
    JournalNeurogastroenterology and Motility
    Volume28
    Issue number8
    DOIs
    Publication statusPublished - 1 Aug 2016

    Keywords

    • colon transit
    • constipation
    • gastrointestinal transit
    • loperamide
    • prucalopride

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