Development of tolerance to the stimulatory effect of morphine in dog intestine

Intestinal motor responses to morphine and 5-hydroxytryptamine (5-HT) were measured in dogs injected daily for 16 days with morphine (stabilized at 30 mg/kg i.v.) and compared to responses obtained in control animals. Intestinal contractions produced by 10 and 20 μg/kg morphine were reduced in the morphine-treated animals. Responses to 5-HT did not differ between the two groups. The contractor dose-response curve for morphine, but not for 5-HT or bethanechol, was shifted markedly to the right in intestinal segments isolated from morphine-treated dogs. It is concluded that tolerance to the intestinal stimulatory effect of morphine occurs in the dog.