The involvement of histamine receptors in morphine-induced increased naloxone potency in mice

In the present study, the effect of histamine agonists and antagonists on morphine antinociception and naloxone antagonism were studied. The antinociceptive effect of morphine and the antagonistic effect of naloxone were measured by the acetic acid-induced abdominal constriction test in mice. It was found that pretreatment with 2-methylhistamine, a histamine H1-receptor agonist, altered neither the antinociceptive effect of morphine nor the antagonistic effect of naloxone. When 2-methylhistamine was given together with morphine as pretreatment, the naloxone potency was enhanced compared with pretreatment by morphine alone. Pretreatment with 2-pyridylethylamine, another histamine H1-receptor agonist, alone or in combination with morphine, altered neither the antinociceptive activity of morphine nor the antagonistic potency of naloxone. Pretreatment with 4-methylhistamine, a histamine H2-receptor agonist, did not alter the antinociceptive activity of morphine or the antagonistic effect of naloxone. However, when given together with morphine as the pretreatment, the antinociceptive effect of morphine as well as the antagonistic activity of naloxone were enhanced. Similar effects were observed with dimaprit, another histamine H2-receptor agonist. Pretreatment with diphenhydramine, a histamine H1-receptor antagonist, alone or in combination with morphine, altered neither the antinociceptive effect of morphine nor the antagonistic activity of naloxone. Pretreatment with cimetidine, a histamine H2-receptor antagonist, did not affect the antinociceptive effect of morphine and the antagonistic potency of naloxone. However, when given together with morphine as pretreatment, it suppressed the ability of morphine in inducing an increase in naloxone potency. Similar effects were observed with ranitidine, another histamine H2-receptor blocker.(ABSTRACT TRUNCATED AT 250 WORDS)