Background The antineoplastic drug 5‐fluoruracil (5‐FU) is a pirimidine analog, which frequently induces potentially fatal diarrhea and mucositis. Cannabinoids reduce gastrointestinal motility and secretion and might prevent 5‐FU‐induced gut adverse effects. Here, we asked whether cannabinoids may prevent diarrhea and mucositis induced by 5‐FU in the rat. Methods Male Wistar rats received vehicle or the non‐selective cannabinoid agonist WIN 55,212‐2 (WIN; 0.5 mg kg−1 injection−1, 1 injection day−1, 4 consecutive days) by intraperitoneal (ip) route; on the first 2 days, animals received also saline or 5‐FU (150 mg kg−1 injection−1, cumulative dose of 300 mg kg−1). Gastrointestinal motor function was radiographically studied after barium contrast intragastric administration on experimental days 1 and 4. Structural alterations of the stomach, small intestine and colon were histologically studied on day 4. PAS staining and immunohistochemistry for Ki67, chromogranin A and CD163 were used to detect secretory, proliferating, and endocrine cells, and activated macrophages respectively. Key Results As shown radiographically, 5‐FU induced significant gastric emptying delay (on days 1 and 4) and diarrhea (on day 4). WIN did not significantly alter the motility curves obtained for either control or 5‐FU‐treated animals but tended to reduce the severity of 5‐FU‐induced diarrhea and increased permanence of barium from day 1 to the beginning of day 4 in 5‐FU‐treated animals. 5‐FU‐induced mucositis was severe and not counteracted by WIN. Conclusions and Inferences 5‐FU‐induced diarrhea, but not mucositis, was partly prevented by WIN at a low dose. Cannabinoids might be useful to prevent chemotherapy‐induced diarrhea.

Background Non‐invasive methods to study gastrointestinal (GI) motility are of high interest, particularly in chronic studies. Amongst these, radiographic techniques after contrast intragastric administration may offer many advantages. In previous studies, we have successfully and reproducibly applied these techniques together with a semiquantitative analysis method to characterize the effect of different drugs, acutely or repeatedly administered in rat models, but we have never before used these techniques in mice. These are very convenient in basic research. Our aim was to determine if our method is also valid in mice. Additionally, we determined the effect of morphine on GI motor function in both species. Methods Animals received an intraperitoneal administration of morphine (at 10 and 5 mg/kg for rats and mice, respectively). Twenty min later, barium contrast (at 2 g/mL) was gavaged (2.5 and 0.4 mL for rats and mice respectively) and serial X‐rays were obtained 0–8 h after contrast. X‐rays were analyzed as previously described, using a semiquantitative score to build motility curves for each GI region. Key Results Motility was much faster in mice than in rats for all GI regions. Morphine at the doses used significantly depressed motility in both species to a similar extent if the whole gut or the upper GI regions (stomach, small intestine) were considered, although its effect seemed to be more intense in the lower GI regions (caecum, colorectum) in rats than in mice. Conclusions & Inferences We have validated our X‐rays method for its use in mice.