Evidence for opiate tolerance in newborn rats

It has been reported that tolerance to the antinociceptive effect of morphine does not develop in rats younger than 15 days of age. This may be due to a masking effect of rapidly proliferating opiate receptors during the first 2 postnatal weeks. Newborn rats received morphine (20 mg/kg) or equivolume saline on postnatal days 5, 6, 7, 8 and antinociception was assessed on each day. On day 9, animals of both groups were injected with 0, 0.25, 0.50, 1, 2, 4, 8 or 20 mg/kg of morphine. Antinociception, tested by the tail-flick method, did not diminish over days 5-8, yet on day 9 a rightward shift in the dose-response curve occurred. Thus, tolerance in rats occurs to morphine induced antinociception earlier than 15 days postnatally.