Morphine antinociception is mediated through a LiCl-sensitive, IP3-restorable pathway.
Pretreatment (18 h) of mice with a single s.c. injection of LiCl (10 mmol/kg) reduced the antinociceptive action of centrally administered (i.c.v.) morphine in the tail-flick test (ED50 = 7.7 micrograms) compared to vehicle-treated controls (ED50 = 1.8 micrograms). The coadministration of inositol-1,4,5-trisphosphate (IP3; 20 micrograms) with morphine restored the morphine-induced antinociception (ED50 = 2.4 micrograms) in LiCl-pretreated mice to control levels. These finding implicate a LiCl-sensitive (possibly phosphoinositide) second messenger pathway in the mediation of morphine-induced analgesia.
Raffa
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Drug Discovery Research, R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.
Martinez
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RP
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D008094:Lithium / Q000008:administration & dosage / Q000494:pharmacology*; D018021:Lithium Chloride; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects
D000700:Analgesics; D002712:Chlorides; D009020:Morphine; D015544:Inositol 1,4,5-Trisphosphate; D008094:Lithium; D018021:Lithium Chloride