The differential effects of histamine receptor antagonists on morphine- and U-50,488H-induced antinociception in the mouse

Abstract

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°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.