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KL McGilliard and AE Takemori
Mice were pretreated either acutely or chronically with morphine to test the effect of such pretreatments on the antagonism by naloxone of morphine-induced respiratory depression and analgesia and to compare the development of tolerance to the two effects. A s.c. injection of 20 mg/kg of morphine 6 hr before testing produced a shift of the apparent pA2 of morphine-naloxone for analgesia from 7.05 to 7.33, while the same pretreatment did not change the apparent pA2 for respiratory depression. However, s.c. implantation of a morphine pellet for 72 hr produced a shift in the apparent pA2 of morphine-naloxone for respiratory depression from 7.35 to 7.63, which represents less than a 2-fold increase in naloxone potency. The same pretreatment produced a further shift of the apparent pA2 for analgesia to 7.58, representing a greater than 3-fold increase in naloxone potency. After morphine pellet implantation mice showed a much greater degree of tolerance to morphine- induced analgesia than to respiratory depression. These results provide further evidence that narcotic-induced respiratory depression and analgesia are mediated by different receptor interactions.
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