Morphine Tolerance in the Mouse Ileum and Colon

Repeated administration of morphine is associated with toler-ance to its antinociceptive properties. However, constipation remains the major side effect of chronic exposure to morphine. In contrast, previous studies suggest that tolerance to opioids develops in the ileum of several species. In this study, we provide evidence that constipation may arise due to a lack of tolerance development to morphine in the colon. Mice received implants with either placebo or 75 mg of morphine pellets, and they were examined for morphine tolerance to antinociception, defecation, and intestinal and colonic transit after 72 h. Tissues were obtained from the ileum and distal colon, and contractile responses were measured from longitudinal and circular mus-cle preparations. In morphine-pelleted mice, a 5.5-fold toler-ance developed to antinociception after 72 h, and a 53.2-fol