Prenatal administration of morphine to the rat: tolerance to the analgesic effect of morphine in the offspring.
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 to 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 weeks 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 doeses 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-week-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. It is concluded that 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.
D000375:Aging; D000698:Analgesia; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D004361:Drug Tolerance; D005260:Female; D005865:Gestational Age; D007981:Levorphanol / Q000494:pharmacology; D008431:Maternal-Fetal Exchange; D009020:Morphine / Q000008:administration & dosage* / Q000032:analysis / Q000097:blood; D011247:Pregnancy; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D007981:Levorphanol; D009020:Morphine