Centrally mediated inhibition of small intestinal transit and motility by morphine in the rat.

The effects of morphine treatment on small intestinal propulsion and contractile activity were investigated in unanesthetized rats. Intragastrically, s.c. and i.c.v. administered morphine produced dose-related decreases in the transit of a radioactive marker (51Cr) through the small intestine. Morphine was most potent after i.c.v. administration whereas the intragastric route was the least potent. Intracerebroventricular and s.c. morphine also delayed gastric emptying of [3H]polyethylene glycol placed directly into the stomach. Intragastric morphine at doses up to 500 mg/kg did not alter gastric emptying. The antitransit effects of i.c.v. and s.c. morphine were antagonized by prior treatment with naloxone (2 mg/kg s.c.). Changes in small intestinal motility resulting from morphine treatment were measured directly through chronically implanted silastic cannulas. Two cannulas were implanted in each rat, one into the duodenum and the second in the proximal jejunum. Each cannula was perfused with distilled water at a low flow rate (0.04 ml/min) and increases in intraluminal pressure associated with contractions were recorded as changes in outflow resistance. Morphine treatment decreased the frequency of contractions in both areas of the small intestine. Intracerebroventricular morphine again was the more potent route of administration when compared to s.c. morphine. These data indicate that morphine can act within the central nervous system to alter autonomic outflow to the small intestine. The result is an inhibition of motility which accounts for the antitransit effects of opiate-like compounds in the rat.