The involvement of histamine H2-receptors in restraint-induced antinociception in male mice.

Restraint for 1 h induced significant antinociceptive activity in male mice assessed by the hot-plate test at 55 degrees C. The antinociceptive activity was significant throughout the 1-h period of observation. Prior administration of the histamine H2-receptor agonist dimaprit further enhanced the antinociceptive activity. Furthermore, the induction of antinociception by restraint was antagonized by prior administration of the histamine H2-receptor blocker cimetidine. Similar findings were obtained with another histamine H2-receptor blocker, zolantidine, which supposedly crosses the blood-brain barrier. On the other hand, prior administration of 2-pyridylethylamine, a histamine H1-receptor agonist, or mepyramine, a histamine H1-receptor antagonist, did not affect the development of antinociceptive activity induced by restraint. The doses of histamine receptor agonists and antagonists used in the present study had no effect on the hot-plate response of non-restraint control animals. These results suggest that histamine H2-receptors may be involved in the restraint-induced antinociceptive activity in mice.