Tolerance to the effects of morphine on intestinal motility of unanesthetized dogs
Weisbrodt, N.W.; Thor, P.J.; Copeland, E.M.; Burks, T.F.
Journal of Pharmacology and Experimental Therapeutics 215(2): 515-521
1980
ISSN/ISBN: 0022-3565 PMID: 7192315 Document Number: 154954
Whether tolerance developed to the intestinal stimulatory effects of morphine and/or whether the fasted pattern of motility showed signs of dependence during chronic administration of morphine was studied. Dogs were implanted with electrodes on the serosal surface of the small intestine. After recovery from operation, the fasted pattern of motility and the responses to bolus administrations of morphine sulfate (30, 100 and 300 .mu.g/kg) were determined in each animal. Each animal then was placed on continuous administration of morphine sulfate in dosages of 1.25-40 mg/kg per day. Patterns of motility and responsiveness to bolus doses were determined at each dose level. The continuous infusion of morphine of morphine then was stopped abruptly and the patterns of motility and responsiveness to bolus administration of morphine again were determined. During control periods, each animal demonstrated a distinctive pattern of motility. Bolus administration of morphine caused a dose-dependent increase in contractile activity. Continuous administration of morphine brought about a temporary disruption of the fasted pattern of motility. This pattern returned toward normal when the same daily dose of morphine was maintained for several days. During continuous administration of morphine, the stimulatory effect of the bolus doses was lost. Abrupt withdrawal of the continuous administration of morphine disrupted the normal fasted pattern of motility for 1-2 wk. During this time, there was a rapid return of the stimulatory effects of bolus administration of morphine. Tolerance and physical dependence of the small intestine of unanesthetized dog develops to morphine.