Contrasting influences of 5-hydroxytryptamine receptors in nitrous oxide antinociception in mice.
5-Hydroxytryptamine (5-HT) mechanisms may play a role in opioid-mediated antinociception. Since opioid mechanisms have been implicated in nitrous oxide antinociception, this study was conducted to determine the possible role of 5-HT receptors in nitrous oxide antinociception. Male Swiss Webster mice were pretreated with one of two 5-HT receptor blockers and then tested in the acetic acid abdominal constriction test for their antinociceptive response to nitrous oxide, the kappa-opioid agonist U-50,488H, or the mu-opioid agonist sufentanil. Results indicate that the 5-HT3 receptor blocker ICS-205,930 antagonized both nitrous oxide and U-50,488H effects but not that of sufentanil. Mianserin, a 5-HT1c/5-HT2 receptor blocker, effects but not that of sufentanil. Mianserin, a 5-HT1c/5-HT2 receptor blocker, potentiated effects of both nitrous oxide and U-50,488H but not that of sufentanil. These findings show similarities in nitrous oxide and U-50,488H antinociception and further support our hypothesis that nitrous oxide works through central kappa-opioid mechanisms in mice. The results also suggest different roles for 5-HT receptor subtypes in mediating or modulating the antinociceptive effect of nitrous oxide.
Mueller
J L
JL
Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford 61107.
Quock
R M
RM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009609:Nitrous Oxide / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D017409:Sufentanil
D000700:Analgesics; D011759:Pyrrolidines; D011985:Receptors, Serotonin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D017409:Sufentanil; D009609:Nitrous Oxide; D005283:Fentanyl