Increased antagonist potency of naloxone caused by morphine pretreatment in mice.

Using the writhing test in mice, it was shown that pretreatment with a single dose of morphine hydrochloride given 3 h previously caused a marked increase in the antagonistic effect of naloxone without any change in the antinociceptive action of morphine itself. It was shown that when mice were pretreated with different doses of either morphine alone, or in combination with naloxone, so that each treatment produced the same antinociceptive effect, the increase in naloxone potency was proportional only to the antinociceptive effect of the pretreatment and not to the total dose of morphine present. It was also found that the concurrent administration of naloxone plus morphine prevented the development of "acute dependence" to morphine, as measured by the jumping reaction after challenge with naloxone.