The effect of neonatal exposure to chronic footshock on pain-responsiveness and sensitivity to morphine after maturation in the rat.

Rat pups in 3 groups respectively were given daily footshock, exposure to a footshock apparatus without shock, or no handling from birth to 21 days of age and reared with no manipulation afterwards. After maturation (90-100 days of age), they were assessed for hot-plate paw-lick latency, morphine-induced analgesia and opiate receptor binding assay. In footshocked animals, a significant increase was found in paw-lick latency and in antinociceptive effects of morphine (1.25, 2.5, and 5.0 mg/kg) in comparison with two control groups. The antinociceptive effect of morphine in all 3 groups was antagonized by pretreatment with naloxone (2.0 mg/kg). No significant difference was found in binding activities (Bmax and Kd) for both [3H]naloxone and [3H]Dala2, D-Leu5-enkephalin between the 3 groups. These results suggest that exposure to footshock stress in the preweanling period has a long-term effect on the sensitivity of rats to painful events, probably due to chronic functional changes in endogenous opiate systems at presynaptic level rather than in postsynaptic opiate receptor binding activity.