Morphine treatment at different infant ages: influence on later morphine effects in rats

Evidence suggests that opiate receptor development plays a role in morphine-induced analgesia. From birth to about 15 days of age in rats, there is a concomitant increase in number of opiate receptors and morphine-induced analgesic effect with virtually no change in blood-brain barrier maturation. The present two experiments examined possible age-related changes in tolerance to morphine-induced analgesic, hypoactive, and hyperthermic effects during this period;In Experiment 1, rats were administered either morphine (1 mg/kg), saline, or no treatment at one day of age. At 26 days, one half of the animals from each infant treatment group received morphine (5 mg/kg) and the other half received saline. All animals were then assessed for pain responsivity, activity and body temperature. This injection-test procedure was repeated at 27 and 28 days of age. At 29 days of age, all animals received morphine and were similarly tested. Rats treated with morphine one day after birth subsequently displayed tolerance to morphine-induced analgesic and hypoactive effects, but not to hyperthermic effects. Infant saline-treated animals displayed less activity and higher body temperatures than infant untreated animals;In Experiment 2, rats were administered either morphine (1 mg/kg) or saline at 1, 5, 9 or 13 days of age. At 26 days of age, one half of each infant treatment group received morphine (5 mg/kg) and the other half received saline. Injections and tests for pain responsivity, activity, and body temperature were similar to those of Experiment 1. Animals treated with morphine at 1 but not at 5, 9, or 13 days of age displayed tolerance to morphine-induced analgesic and hypoactive effects. Animals treated with saline early in infancy displayed less pain responsivity and activity than animals treated with saline late in infancy;These results indicate that single-dose tolerance to 1 mg/kg morphine in infants is age-dependent. Age-dependent changes in susceptibility to single-dose morphine tolerance may reflect a change in either blood-brain barrier or opiate receptor development. Furthermore, these results indicate that saline injection in infancy may produce stress-related changes in later pain responsivity, activity, and body temperature