Characteristics of mu and delta opioid binding sites in striatal slices of morphine-tolerant and -dependent mice.
Previously, we demonstrated the enhanced affinity of opioid receptors for naloxone in striatal slices from morphine-dependent mice. In our present study, binding characteristics of the mu opioid receptor agonists, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO) and dihydromorphine, the delta opioid receptor agonist, [D-Ala2, D-Leu5]enkephalin (DADLE), and the opioid antagonist, naloxone, were examined in striatal slices from morphine-tolerant and -dependent mice. Striatal slices from mice that were implanted with a morphine pellet for 3,7 and 21 days displayed significant decreases in Kd values (5.1, 4.6 and 5.5 nM, respectively) of [3H]DAMGO when compared to those in slices from control animals that were not implanted or implanted with placebo pellets (9.6 and 9.3 nM, respectively). Also, a significant increase in the binding affinity of naloxone, but not that of dihydromorphine, was observed in striatal slices of mice that were implanted with a morphine pellet for 3 days. Significant increases in the Bmax of delta binding sites in striatal slices of mice that were implanted with a morphine pellet for 3, 7 and 21 days (20.7, 18.1 and 17.7 pmol/mg tissue, respectively) were observed when compared to that in slices from control mice that were implanted with placebo pellets (11.4 pmol/mg tissue). The enhancement in the binding affinity of DAMGO and naloxone and the increased density of DADLE binding sites paralleled the development of morphine tolerance and dependence and [D-Pen2,D-Pen5]enkephalin cross-tolerance in whole animals. An antinociceptive potentiation between morphine and DAMGO was observed in morphine-tolerant and -dependent mice whereas in naive animals the effects of the two drugs were additive.(ABSTRACT TRUNCATED AT 250 WORDS)
Abdelhamid
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Department of Pharmacology, University of Minnesota, Medical School, Minneapolis 55455.
Takemori
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D000700:Analgesics; D000818:Animals; D001665:Binding Sites; D003342:Corpus Striatum / Q000378:metabolism*; D004347:Drug Interactions; D004361:Drug Tolerance; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism*; D009270:Naloxone / Q000378:metabolism / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*
D000700:Analgesics; D004745:Enkephalins; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine