PRENATAL ADMINISTRATION OF MORPHINE TO RAT - TOLERANCE TO ANALGESIC EFFECT OF MORPHINE IN OFFSPRING

  • 1 January 1976
    • journal article
    • research article
    • Vol. 197  (3) , 533-544
Abstract
The analgesic activity of morphine was assessed by the hot-plate technique in the offspring of female CFE rats that had received morphine twice daily on days 5-12 of pregnancy. A dose of 5.0 mg/kg of morphine was administered for the first 3 injections; 10 mg/kg was used for each of the remaining 13. Morphine dose-response curves were determined in the offspring at 5 wk of age. The analgesic effect of morphine in the offspring of morphine-treated females (morphine offspring) was attenuated by as much as 50% compared to the offspring of saline-treated females (saline offspring). This same relationship between the morphine and saline offspring was also observed in offspring rendered tolerant to the analgesic effect of morphine. A diminished analgesia in the morphine offspring compared to the saline offspring was also observed after the injection of graded doses of levorphanol in both nontolerant and morphine-tolerant offspring. The analgesic effect of a single dose of morphine was also attenuated in 3, 5 and 11 wk old morphine offspring. No differences were found in either brain or plasma concentration of morphine between the morphine and saline offspring. The long-term effect of prenatal morphine administration could not be explained on the basis of maternal influences since cross-fostering procedures failed to abolish it. The administration of moderate doses of morphine to gestating rats can induce a long-lasting tolerance to the analgesic effect of morphine in the offspring. The results may have far-reaching implications in view of the current popularity of drug maintenance programs for the treatment of narcotic addiction in women of child-bearing age.