A Gi2alpha antisense oligonucleotide differentiates morphine antinociception, constipation and acute dependence in mice.
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.
Raffa
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Drug Discovery Research, The R.W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA.
Goode
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Martinez
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Jacoby
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HI
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
D000701:Analgesics, Opioid; D016376:Oligonucleotides, Antisense; D009270:Naloxone; D009020:Morphine; D019204:GTP-Binding Proteins