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Nitrous oxide antinociception in rats was evaluated by the warm water tail withdrawal test following central pretreatment with blockers of various opioid receptor subtypes. The analgesic dose, 50% (AD50) value for nitrous oxide antinociception was significantly elevated by MR-2266 (which is relatively selective for kappa-opioid receptors) and increased to a lesser degree by ICI-174,864 (which is selective for delta-opioid receptors). However, pretreatment with beta-funaltrexamine (which is selective for mu-opioid receptors), even at extremely high doses, was ineffective in altering the AD50 for nitrous oxide antinociception. According to these findings, nitrous oxide antinociception, as evaluated in this paradigm, appears to be mediated by kappa- and possibly delta- but not mu-opioid receptors.
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