title: A Gi2alpha antisense oligonucleotide differentiates morphine antinociception, constipation and acute dependence in mice.
abstract: In the same mice in which the intracerebroventricular (i.c.v.) administration of antisense oligodeoxyribonucleotide (oligo) directed against the Gi2alpha (but not Gi1alpha, Gi3alpha or G(s)alpha) G-protein subunits attenuated i.c.v. morphine-induced antinociception in the tail-flick test, none of the oligos altered naloxone-precipitated jumping (acute dependence). Likewise, none of the oligos significantly altered morphine-induced constipation. Hence, i.c.v. morphine-induced antinociception might be preferentially mediated via transduction pathway(s) different from constipation or acute dependence, offering novel opportunities for drug discovery.
authors.affiliation: Drug Discovery Research, The R.W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Raffa
authors.forename: T L
authors.initials: TL
authors.lastname: Goode
authors.forename: R P
authors.initials: RP
authors.lastname: Martinez
authors.forename: H I
authors.initials: HI
authors.lastname: Jacoby
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D003248:Constipation / Q000139:chemically induced / Q000503:physiopathology*; D019204:GTP-Binding Proteins / Q000235:genetics*; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain; D011930:Reaction Time / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D016376:Oligonucleotides, Antisense; D009270:Naloxone; D009020:Morphine; D019204:GTP-Binding Proteins