The ontogeny of opiate tolerance and withdrawal in infant rats.

The acquisition of morphine analgesic tolerance was investigated in neonatal rats. Morphine was found to produce a potent analgesia, as measured by latency to retract a hindpaw from a 52 degree C hotplate, in rat pups as young as 1 day of age. Morphine analgesic tolerance, however, did not develop in rats until the third week of life. Rats given the same daily morphine regimen starting at 15 days of age or older showed rapid tolerance development. The data from four experiments indicate that experience with morphine prior to this age (Day 15) does not impact on the analgesic efficacy of the drug. Similarly, when morphine treatment was discontinued and the rats given a naloxone challenge, withdrawal symptoms were not observed in very young rats. Opiate withdrawal was first detected in rats that started their daily morphine treatment at 30 days of age and were then challenged with naloxone at 52 days of age. Therefore, two correlates of opiate addiction, tolerance and withdrawal, appear to be relatively late-developing phenomena in the rat.