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

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 antagonized the analgesic effect of morphine and the development of tolerance to and dependence on morphine, dose dependently. The time course of the development of tolerance to a single dose of morphine almost paralleled that of dependence on morphine but the time course of the disappearance of tolerance did not coincide with that of dependence. When start of the duration of action of morphine was blocked by naloxone for various time intervals, 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 was completely antagonized by naloxone.