Differences in morphine-induced antinociception and locomotor activity in mature adult and aged mice

Mature adult (3-6 months old) and aged (24-27 months old) male ICR mice were injected with 10 to 100 mg/kg morphine, SC. The ED50 values for locomotor behavior representing 5 times control activity were 7.5 mg/kg for aged mice and 17.8 mg/kg for the mature adults. There were striking age- and dose-dependent differences in both intensities and durations of morphine-induced locomotor activity. The ED50 values for antinociception 1 hour after morphine administration were 70 mg/kg for the aged mice and 13 mg/kg for the mature adults. One hour after injecting 30 and 100 mg/kg morphine tagged with 3H-morphine, 0.13 and 0.14 percent of the doses appeared in brains of aged and mature adult mice, respectively. Distribution of morphine among brain regions was the same for both age groups. The results suggest that the differences in response to morphine by the two age groups were due to age-related differences in affinities, numbers and/or functioning of opioid receptors and not to pharmacokinetic differences.