MORPHINE ANALGESIA AND CEREBRAL OPIATE RECEPTORS: A DEVELOPMENTAL STUDY

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Abstract
1 Development of the analgesic response to morphine and ontogenesis of central opiate receptors were analyzed in rats 5 to 120 days old. 2 The analgesic effect of morphine increased until day 15, after which it decreased to reach a plateau at about day 30. With phenoperidine, on the other hand, the analgesic effect increased until day 15, remained constant between day 15 and day 30 after which it decreased slowly. 3 The ratio of the amounts of morphine in blood over those in brain increased about 3 fold between day 15 and day 30. 4 Opiate receptors were detected in the brain of newborn rats: stereospecific binding of [3H]-naloxone at 10 and 50 nM indicated the presence of low and high affinity binding sites. 5 The number of [3H]-naloxone binding sites increased rapidly during the second and third week after birth. Their affinity for several opiates remained constant throughout development. 6 These results indicate that the analgesic activity of opiates varies with age: until day 15, the analgesic effect of opiates increases in parallel with the number of opiate brain receptors. Then, the formation of the blood brain barrier introduces an additional step in the regulation of opiate activity.