Ontogeny of opioid pharmacology and receptors: high and low affinity site differences.

The development of the high affinity binding of a variety of opiates and enkephalins is distinct from low affinity binding. During the first 2 weeks after birth, low affinity binding in both brain and spinal cord remains relatively constant while high affinity binding increases up to 3-fold. Differences in the development of analgesic and respiratory sensitivity to opiates are also found. Whereas morphine, beta-endorphin and D-Ala2-Met5-enkephalin-amide depress respiratory rates in 2-day old rats at doses equal to or lower than those active in 14-day old rats, morphine's analgesic ED50 is 40-fold greater in 2-day old than in 14-day old rats. Similarly, beta-endorphin and D-Ala2-Met5-enkephalinamide are analgesic in 14-day old rats but not 7-day old rats. The small effect of spinal transections on morphine analgesia in 14-day old rats suggests that the change in analgesic sensitivity is at a segmental spinal level and not a result of descending pathways. These results suggest an interesting correlation between high affinity binding and analgesia and between low affinity binding and respiratory effects.