title: Alterations in the antagonism by naloxone of morphine-induced respiratory depression and analgesia after morphine pretreatment.
abstract: 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.
mesh_terms: D000700:Analgesics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000378:metabolism / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000700:Analgesics; D004343:Drug Implants; D009270:Naloxone; D009020:Morphine