Dose-dependent antagonism and potentiation of nitrous oxide antinociception by naloxone in mice.
Administration of the anesthetic gas nitrous oxide (N2O) evoked a concentration-dependent antinociceptive effect in mice as assessed by the abdominal constriction test. Depending on the dose and route of pretreatment with the opioid receptor blocker naloxone, the N2O drug effect was either antagonized or potentiated. After s.c. pretreatment with milligram per kilogram doses of naloxone, dose-related antagonism occurred; picogram per kilogram doses potentiated N2O-induced antinociception. The i.c.v. pretreatment with microgram quantities of naloxone also antagonized N2O antinociception in a dose-related fashion; i.c.v. pretreatment with femtogram doses was without effect. On the other hand, intrathecal (i.t.) pretreatment with femtogram quantities of naloxone potentiated N2O antinociception; i.t. pretreatment with microgram quantities continued to antagonize the antinociceptive effect. The same pattern of interaction was observed in mice challenged with the kappa opioid analgesic drug trans (+- 3,4-dichlow-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide methane sulfonate (U-50, 488H) after s.c., i.c.v. or i.t. pretreatments with high and low doses of naloxone. These results 1) demonstrate further similarities in the opioid receptor mediation of N2O and U-50, 488H antinociceptive effects and also 2) support the concept of high-affinity spinal opioid receptors, whose blockade by s.c.- or i.t.- but not i.c.v.-administered low-dose naloxone can potentiate the antinociceptive effects of both N2O and U-50,488H. These findings suggest that the antinociceptive effect of N2O might be modulated by a descending opioid system that inhibits analgesia.
Quock
R M
RM
Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford.
Curtis
B A
BA
Reynolds
B J
BJ
Mueller
J L
JL
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D004357:Drug Synergism; D008297:Male; D051379:Mice; D009270:Naloxone / Q000008:administration & dosage*; D009609:Nitrous Oxide / Q000008:administration & dosage*; D009619:Nociceptors / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000187:drug effects*
D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009609:Nitrous Oxide