Etonitazene-induced antinociception in mu1 opioid receptor deficient CXBK mice: evidence for a role for mu2 receptors in supraspinal antinociception.
The prevailing view is that supraspinal mu opioid-mediated antinociception in mice is mediated via the mu 1 subtype. The purpose of the present study was to determine if the highly mu-selective compound etonitazene could produce supraspinal (intracerebroventricular; i.c.v.) antinociception in CXBK mice, which are deficient in brain mu1, but not mu2, opioid receptors. CXBK or normal Crl:CD-1 (ICR)BR mice were administered graded doses of etonitazene i.c.v. and 15 min later antinociception was assessed by a standard radiant-heat or 55 degrees C water tail-flick test. Etonitazene produced dose-related antinociception that was blocked by naloxone and by beta-FNA (demonstrating a mu opioid mechanism), but not by either ICI-174,864 or naltrindole (demonstrating the lack of involvement of delta opioid receptors). These findings suggest that mu2 opioid receptors are important contributors to opioid-induced supraspinal antinociception in mice.
Connelly
C D
CD
R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477.
Martinez
R P
RP
Schupsky
J J
JJ
Porreca
F
F
Raffa
R B
RB
D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004743:Enkephalin, Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D006358:Hot Temperature; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D017450:Receptors, Opioid, mu / Q000172:deficiency* / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D001562:Benzimidazoles; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004743:Enkephalin, Leucine; D009271:Naltrexone; C024524:beta-funaltrexamine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; C055382:naltrindole