Antagonism by naloxone of tolerance and dependence in mice given a single dose of morphine

Abstract

The effect of naloxone given at various times after morphine administration on the development of tolerance to and dependence on a single dose of morphine was studied. Naloxone dose dependently antagonized the analgesic effect of morphine and the development of tolerance to and dependence on morphine. The time course of tolerance development to a single dose of morphine paralleled that of morphine dependence but the time course of tolerance disappearance did not coincide with that of dependence. When start of the duration of action of morphine was blocked by naloxone for various time interval the degree of tolerance to and dependence on morphine was antagonized time dependently. When the end of the duration of action of morphine was antagonized by naloxone for various time intervals tolerance and dependence which developed up to that time were antagonized by naloxone.