Development of tolerance to morphine and pethidine in rats in dependence on age

The development of tolerance to the analgesic effect of morphine (10 mg/kg.i.p.) and to pethidine 40 mg)/kg i.p.), given every 3 hours 13 times in succession or every 6 or 24 hours 7 times in succession, was studied in rats of different age groups (21 days, 42 days, 3 months and 18 months old). Pain threshold was determined by electric algic stimulation. The rate of tolerance development to the analgetic effect of morphine and pethidine decreased with age and changed only slightly with the frequency of application. In young animals (21 days old) the analgesic effect was very intensive after the first application of pethidine as well as morphine, after further applications the analgesic effect was reduced sharply until its complete disappearance. In animals aged 42 days and 3 months the analgesic effect was not so strong after the first applicaion but the decrease, too, was slower. In 18 months old animals the analgesic effect after the first dose was high and declined very moderately after further doses. It is assumed that the development of tolerance to the effect of strong analgesics is related to the rate of protein synthesis in the central nervous system.