Central and peripheral inhibitory effects of morphine on intestinal transit in mice

In the present study, intestinal motility was measured by the transit of charcoal meal through the small intestine in mice. Morphine, given subcutaneously, caused a dose-dependent slowing of the rate of intestinal transit. This inhibitory effect of morphine was antagonised by prior subcutaneous administration of naloxone hydrochloride or its quaternary analog naloxone methylbromide. However, on a weight basis, naloxone methylbromide was only about half as potent as naloxone hydrochloride. Morphine given centrally, either intracerebroventricularly or intracisternally, caused a dose-related inhibition of intestinal transit, the intracerebroventricular route appearing to be more effective. The effects of centrally administered morphine were antagonised by prior subcutaneous administration of naloxone hydrochloride but not by naloxone methylbromide. The narcotic antagonists administered centrally were effective in suppressing the inhibitory effect of subcutaneously administered morphine. When given intracerebroventricularly naloxone methylbromide was as effective as naloxone hydrochloride, while by intracisternal route, it was about half as potent as naloxone hydrochloride. These results provide evidence that peripherally administered morphine inhibits intestinal transit by both central and peripheral mechanisms. Of the central routes of administration studied, it appears that the sites around the lateral ventricles play a more significant role in the intestinal inhibitory actions of morphine.