title: dextro- and levo-morphine attenuate opioid delta and kappa receptor agonist produced analgesia in mu-opioid receptor knockout mice.
abstract: We have demonstrated that the antianalgesia induced by dextro-morphine and levo-morphine is not mediated by the stimulation of mu-opioid receptors in male CD-1 mice. We now report that the dextro-morphine and levo-morphine attenuated antinociception produced by delta-opioid receptor agonist deltorphin II and kappa-opioid receptor agonist U50,488H given spinally in the male mu-opioid receptor knockout mice. The tail-flick response was used for the antinociceptive test. Intrathecal injection of levo-morphine (3 nmol) markedly inhibited the tail-flick response in wild type, partially in heterozygous, but not in homozygous mu-opioid receptor knockout mice. Intrathecal pretreatment with dextro-morphine (33 fmol) or levo-morphine (0.3 nmol) for 45 min also attenuated levo-morphine-produced antinociception in wide type mice. Intrathecal pretreatment with dextro-morphine (33 fmol) or levo-morphine (0.3 nmol) for 45 min attenuated the tail-flick inhibition produced by deltorphin II (12.8 nmol) and U50,488H (123.3 nmol) in wide type, heterozygous and homozygous mu-opioid receptor knockout mice. The findings provide additional evidence that mu-opioid receptors are not involved in the antianalgesia induced by dextro-morphine and levo-morphine.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Hsiang-en
authors.initials: HE
authors.lastname: Wu
authors.forename: Han-Sen
authors.initials: HS
authors.lastname: Sun
authors.forename: Maia
authors.initials: M
authors.lastname: Terashivili
authors.forename: Emma
authors.initials: E
authors.lastname: Schwasinger
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: F Scott
authors.initials: FS
authors.lastname: Hall
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.forename: Leon F
authors.initials: LF
authors.lastname: Tseng
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D005260:Female; D005838:Genotype; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000503:physiopathology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000502:physiology; D013237:Stereoisomerism
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C060209:deltorphin II, Ala(2)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine