Transgenic superoxide dismutase mice differ in opioid-induced analgesia.
Autoradiographic data from transgenic mice carrying the human Cu/Zn-superoxide dismutase gene demonstrate an increase in mu-opioid receptor concentration in dopaminergic-related areas and the central grey area. The relative potencies of mu-, delta- and kappa-opioid receptor agonists to induce antinociception in heterozygous and homozygous superoxide dismutase transgenic mice as well as four inbred strains were assessed to determine the functional significance of the increased receptor concentration. Increased superoxide dismutase activity results in an increased sensitivity to mu-agonists in a gene dosage-dependent manner. SOD/Tg/hom mice were less sensitive to the delta-agonist than were SOD/Tg/het mice. The superoxide dismutase transgene did not affect kappa-opioid receptor agonist sensitivity. These data suggest that delta-opioid receptors are not regulated in the same manner as mu-opioid receptors and that kappa-opioid receptors are unaffected by superoxide dismutase activity.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009020:Morphine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*
D000700:Analgesics; D004745:Enkephalins; D011759:Pyrrolidines; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D013482:Superoxide Dismutase