Adolescent chronic escalating morphine administration induces long lasting changes in tolerance and dependence to morphine in rats.

Adolescence is a gradual period of transition from childhood to adulthood. It is considered as a sensitive developmental time point that long lasting changes occur in the brain. The present study examined adolescent chronic escalating morphine administration on morphine tolerance and dependence in adulthood. Adolescent male Wistar rats (30days old) were administered increasing doses of morphine (2.5 to 25mg/kg, s.c.) every 12h, for 10days. Control rats received saline according to the same protocol. Thereafter, during adulthood (65-75days old), tolerance to antinociceptive effect of morphine was induced by subcutaneous injection of 3mg/kg morphine, once a day for 7days. Morphine analgesia was measured in the animals by tail flick test every two days, 10min before and 30min after morphine administration. Also, in another test, adult rats were administered morphine (10mg/kg, s.c.) twice a day for 9days to become morphine dependent. On day 10, naloxone (2mg/kg, i.p.) was injected 2h after morphine administration. Somatic signs of morphine withdrawal were then recorded in a clear Plexiglas test chamber for 25min. Results showed that adolescent morphine treatment significantly facilitates the development of tolerance to the analgesic effect of morphine and increases morphine withdrawal signs (grooming, head tremor, sniffing, scratching and teeth chattering) in adulthood compared to the saline group. Facilitation of morphine tolerance and potentiation of withdrawal signs suggests that chronic escalating morphine treatment during adolescence causes long-lasting effects on development of morphine tolerance and dependence in adulthood.