THE DIFFERENTIAL-EFFECTS OF HISTAMINE-RECEPTOR ANTAGONISTS ON MORPHINE-INDUCED AND U-50,488H-INDUCED ANTINOCICEPTION IN THE MOUSE

The effects of thioperamide, an H-3 antagonist, and histamine H-1 and H-2 antagonists (s.c.) on morphine (s.c. or i.c.v.)- and U-50,488H (i.c.v.) induced antinociception in male ddY mice were examined using the hot-plate (55-degrees-C) test. Thioperamide significantly inhibited morphine-induced antinociception, but not U-50,488H-induced antinociception. The suppressive effect of thioperamide on morphine-induced antinociception was reversed by the H-1 antagonist pyrilamine, but not by the H-2 antagonist zolantidine. On the other hand, pyrilamine significantly potentiated the antinociception induced by morphine, but not that induced by U-50,488H. Zolantidine significantly inhibited morphine-induced antinociception in a dose-dependent manner, but not U-50,488H-induced antinociception. Both astemizole, an H-1 antagonist, and ranitidine, an H-2 antagonist, which are known to barely cross the blood brain barrier, did not affect morphine-induced antinociception. These results suggest that morphine-induced antinociception may be potentiated by activation of H-2 receptors and suppressed by activation of H-1 receptors in the brain. Furthermore, neuronal histamine release induced by thioperamide may suppress morphine-induced antinociception through H-1 receptors.