Analgesic cross-tolerance between morphine and opioid peptides.
The analgesic effect of intracerebroventricular administration of morphine, ketocyclazocine, [D-ala2]-methionine enkephalinamide (DAM), [D-ala2-D-leu5]-enkephalin (DADLE), leuenkephalin, metenkephalin, and beta-endorphin on acetic acid-induced abdominal writhing (AAW) was investigated in naive and morphine-tolerant mice. It was found that the relative potencies of a series of opioids are different in naive and morphine-tolerant groups. In naive animals, the order of potency (ED50, nmol) was beta-endorphin greater than morphine = DAM greater than DADLE greater than ketocyclazocine = leuenkephalin = metenkephalin. The morphine-tolerant animals were cross-tolerant to ketocyclazocine and to all the peptides studied; DAM and beta-endorphin exhibited the highest degree of tolerance. In morphine-tolerant animals, the order of potency was morphine = DADLE = beta-endorphin greater than DAM = ketocyclazocine = metenkephalin greater than leuenkephalin. The results indicate that endogenous opioid systems may be affected by tolerance development to morphine.
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D004723:Endorphins / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D000700:Analgesics; D004723:Endorphins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009020:Morphine