The effects of age on the development of tolerance to and physical dependence on morphine in rats.

Changes in growth rate and the development of tolerance and physical dependence during repeated morphine administration were compared in different age groups of rats. Chronic treatment of rats for 3 weeks with increasing doses of morphine resulted in an inhibition of the growth rate of older rats but not of younger rats. The magnitude and time course of the loss of body weight upon morphine withdrawal in morphine-treated rats were independent of the age of the animal. Morphine increased the "pain" threshold in rats as monitored by the electric foot-shock technique. These analgesic effects were greater in 12-week-old rats than in 4- or 7-week-old rats. Repeated administration of morphine resulted in a gradual loss of the analgesic response to morphine in all age groups. However, the rate of development of tolerance to morphine was faster in younger rats than in older rats when these animals were injected repeatedly either with a fixed dose or with equipotent doses of morphine. These investigations indicate that the rate of the development of tolerance to morphine is significantly affected by the age of the subject.