Morphine Analgesia in Rats at Various Ages

: Groups of 8-16 rats at various ages (20, 26, 32, 42 days old and adult animals) were injected subcutaneously with morphine and the degree of analgesia measured, using the hot plate technique, at 30, 60, 90, 120 and 150 min. after the injection. The rise and decline of analgesia war steeper in animals in the younger age groups than in the 42 days old or in the adult animals. The degree of analgesia was thus at a maximum at 30 or 60 min. in the 20, 26 and 32 days old rats, whereas a peak analgesic effect was measured at 60 or 90 min. in the 42 days old and the adult animals. Sensitivity to morphine analgesia was greatest in the youngest age group and then gradually declined towards the adult level. When comparisons were made at the height of analgesia, 7,5-10 times greater doses were required in the adult animals in order to produce a degree of analgesia of the same order of magnitude as that obtained in the 20 days old animals. At the age of 26 days the difference in sensitivity was about threefold and approximately twofold at the age of 32 days. The analgesic effect was very similar in the 42 days old rats and in the adult animals. The high degree of sensitivity to morphine analgesia in the 20 days old animals was matched by very high amounts of morphine in the brain 40 min. after the subcutaneous injection of 5 mg/kg morphine labelled with 14C in the aminomethyl group. The amounts of morphine in the brain of the 26 days old rats were thus less than one half of that found in the brain of the youngest animals. Brain levels of morphine in the 26 days old animals were significantly different from those in the brain of 42 days old and adult rats but not from those found in the brain of the 32 days old animals. The amounts of morphine in the brain of the 32 days old animals did not differ significantly from that found in the 42 days old or in the adult animals. The ratio between the amounts of morphine in plasma versus brain increased gradually with age (20 days old animals: 1.77; adult animals: 3.44). Accessability of morphine to the brain thus decreased with age by a factor of two. It was accordingly concluded that the relatively lower amounts of morphine in the brain could to a certain extent, at any rate, explain the lower sensitivity in the older than in the younger rats. The results also indicate that the sensitivity to morphine analgesia may decrease per se with age. Analgesic experiments with young of mothers treated with morphine late in pregnancy showed that the highest degree of analgesia obtained was the same as that in the respective control young. It was, however, found that analgesia declined faster in the morphine treated young than in the control young in the 20 and 26 days groups (the degree of analgesia was significantly lower at 90 min. in the morphine treated young), whereas this was not the case in the 32 or 42 days old rats. This was taken as a sign of residual tolerance to morphine. Residual tolerance (significantly lower analgesic effect of morphine at 90 and 120 min.) was also observed in the mothers 42 days after delivery, following treatment with morphine during pregnancy. The young of the morphine treated mothers weighed significantly less at the age of 20 and 26 days than the control young. This difference however, was not seen after 4 weeks of age.