| Abstract: |
In contrast to the rapid development of tolerance to morphine in CD-1 mice, tolerance is not seen in 129/SvEv mice implanted with morphine pellets or given daily morphine injections for 5 days. Similarly, the progressive and complete loss of analgesia in CD-1 mice seen with repeated dosing of the delta ligand [D-Pen2,D-Pen5]enkephalin is not observed in 129/SvEv mice. In contrast, tolerance develops normally to both the kappa1 drug U50,488H and the kappa3 agent naloxone benzoylhdrazone. N-methyl-D-aspartate (NMDA) given alone attenuates morphine analgesia in CD-1 mice and accelerates the development of tolerance in CD-1 mice when given daily with morphine. In contrast, NMDA has no significant effect in the 129/SvEv mice in either paradigm. Activation of NMDA receptors can lead to the production of nitric oxide, which also is involved with morphine tolerance. Sodium nitroprusside and L-arginine increase nitric oxide levels and decrease morphine analgesia in both the control CD-1 and 129/SvEv mice. Thus, the defect in the NMDA/nitric oxide cascade responsible for the loss of morphine tolerance in the 129/SvEv mice rests at the level of the NMDA receptor itself or in the steps up to the activation of nitric oxide synthase. |
| Keywords: |
signal transduction; controlled study; dose response; nonhuman; mouse; animals; mice; animal experiment; animal model; mice, inbred strains; morphine; drug sensitivity; analgesia; drug tolerance; arginine; nitric oxide synthase; tail flick test; n methyl dextro aspartic acid receptor; nitric oxide; receptors, opioid, delta; 3,4 dichloro n methyl n [2 (1 pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate; naloxone benzoylhydrazone; antinociception; receptors, n-methyl-d-aspartate; enkephalin; nitroprusside sodium; n methyl dextro aspartic acid; male; priority journal; article; receptors, opioid, kappa; analgesics, non-narcotic; enkephalins; kappa opiate receptor agonist; nitroprusside; 3,4-dichloro-n-methyl-n-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-isomer; enkephalin, d-penicillamine (2,5)-
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