Short-term and delayed behavioral effects of pre- and post-weaning morphine in mice

Ninety mouse pups of the CD-1 outbred strain were used to assess activity (Varimex Activity Meter, Columbus Instr., OH) and analgesia (hot plate) after morphine hydrochloride given IP either on days 14-16 (preweanlings) or on days 21-23 (postweanlings). In preweanlings morphine depressed activity already at the lowest dose tested (0.5 mg/kg), and higher doses (1, 5, and 10 mg/kg) did not produce a significantly larger effect. Activity of postweanlings was not depressed until a very high dose (20 mg/kg). By contrast, morphine produced clear analgesic effects at all doses in both preweanlings (day 14) and postweanlings (day 21). Around day 70, activity and hot-plate tests in the no-drug state showed no differences due to prior treatment, except for the fact that hot-plate latencies of mice previously injected with saline as preweanlings were higher than those of all other groups. Twenty-four hr later the tests were repeated after morphine injection (10 mg/kg), and showed a significantly greater depression of activity in mice previously exposed as preweanlings. On the other hand, all groups previously exposed to morphine at either the pre- or the post-weanling stage showed tolerance to the analgesic effect of the drug. These developmental profiles confirm that opioid systems contribute to the modulation of activity by mechanisms which are at least in part separate from those mediating analgesia.