| Abstract: |
Microinjection of opiates into either the periaqueductual gray, locus coeruleus, nucleus raphe magnus, or nucleus reticularis gigantocellularis elicits a profound naloxone-sensitive analgesia. μ-Opioid receptors have been implicated in supraspinal analgesia and studies from our laboratory have demonstrated the importance of the μ1-receptor subtype. In an effort to examine the receptor subtypes responsible for opioid analgesia in specific brain regions, we examined dose-response relationships and naloxonazine sensitivity of morphine and two enkephalin derivatives in the above 4 brain regions. Both morphine and [d-Ser2, Leu5]enkephalin-Thr6 (DSLET) were effective analgesics in all regions examined. The poor affinity of DSLET for μ2-receptors and of morphine for δ-receptors, combined with their similar, high affinity for μ1-receptors, implied a μ1-mechanism of action. The μ1-selective antagonist naloxonazine effectively blocked the analgesic responses of both compounds in all regions. [d-Pen2,d-Pen5]enkephalin (DPDPE), a potent δ-ligand which does not interact with μ1-receptors, did not elicit analgesia in either the periaqueductal gray or locus coeruleus at any dose tested. These results suggest that opiates and opioid peptides produce analgesia in these 4 brain regions through μ1-receptors. The inactivity of DPDPE argues against a role for δ-receptors and the similar analgesic potencies of morphine and DSLET makes a significant role for μ2-receptors unlikely. © 1988. |
| Keywords: |
unclassified drug; nonhuman; animal; opiate; animal experiment; brain; spinal cord; rat; organ specificity; rats; morphine; oligopeptides; analgesia; brain region; receptors, opioid, mu; intravenous drug administration; injections, intravenous; naloxone; microinjections; opiate receptor; enkephalin[2,5 dextro penicillamine]; cerebral ventricles; receptor subtype; injections, intraventricular; naloxonazine; rats, inbred strains; subcutaneous drug administration; receptors, opioid; male; enkephalin derivative; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; enkephalins; enkephalin, d-penicillamine (2,5)-; intracerebral drug administration; leucine enkephalin[2 serine 6 threonine]
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