Prenatal administration of levorphanol or dextrorphan to the rat: analgesic effect of morphine in the offspring.

We have recently demonstrated that prenatal administration of morphine to the rat results in tolerance to the analgesic effects of morphine in the offspring at 3 to 11 weeks of age. To extend these findings, levorphanol or dextrorphan was administered to female CFE rats during days 5 to 12 of gestation. Control animals were injected with 0.9% saline on the same schedule. At 5 weeks of age all offspring were tested with graded doses of morphine in the hot-plate test for analgesia. Morphine produced a dose-related increase in analgesia in all offspring, but the effect of morphine in the offspring of levorphanol-treated females was significantly reduced compared to the offspring of saline-treated females; the analgesic effect of morphine did not differ between the offspring of the dextrorphan- and saline-treated females. The analgesic effect of morphine remained reduced in 9-week old offspring of levorphanol-treated females compared to the corresponding offspring of females that had received saline. Diminished analgesic activity of morphine in the offspring of levorphanol-treated females compared to the offspring of females that had received dextrorphan or saline was still observed even when the offspring were rendered tolerant to morphine by daily drug injections over a period of 5 days. Thus, the protracted tolerance to the analgesic effects of morphine can also be produced by a morphine congener (levorphanol), but not by its analgesically inactive (+) isomer (dextrorphan).