Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats.
We investigated the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, whether bacterial overgrowth developed in morphine-dependent rats, and the effect of naloxone, 0.5 mg/kg sc, and methylbromide naltrexone, 1.0 mg/kg sc, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. We also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine, 100 micrograms/kg sc. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-[14C]xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in 14CO2 excretion was noted in the morphine-dependent rats. After injection of naloxone, the morphine-dependent rats had a marked increase in spike activity with no identifiable activity fronts for 89 +/- 8 min. Similarly, methylbromide naltrexone disrupted activity fronts, but for a significantly shorter period. Clonidine prevented the marked increase in spike activity that occurred during naloxone-induced withdrawal. We conclude from our studies that myoelectric activity of the small intestine develops incomplete tolerance to morphine; bacterial overgrowth is not a feature of morphine dependence in the rat; alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an alpha 2-adrenergic agonist.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004576:Electromyography; D007421:Intestine, Small / Q000382:microbiology / Q000503:physiopathology*; D009021:Morphine Dependence / Q000503:physiopathology*; D009130:Muscle, Smooth / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D010507:Periodicity; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014994:Xylose / Q000378:metabolism
D009270:Naloxone; D014994:Xylose; D003000:Clonidine