Opiate tolerance/dependence in the isolated guinea pig ileum is associated with an increased sensitivity to acetylcholine.

The number of rhythmic circular muscle contractions elicited by acetylcholine was increased in isolated intestinal segments taken from morphine-tolerant/dependent guinea pigs and exposed in vitro to an adequate normorphine concentration. Segments which underwent a partial withdrawal in vitro showed some degree of supersensitivity to acetylcholine which was, however, not significant. In contrast, basal peristaltic reflex activity was enhanced during a partial opiate withdrawal but not during exposure of the segments to a normorphine concentration high enough to maintain opiate tolerance/dependence. These data suggest that a supersensitivity to acetylcholine participates, at least partially, in the development of tolerance to the inhibitory action of opioids upon intestinal peristalsis.