Effects of a histamine H2 receptor agonist and antagonist on restraint-induced antinociception in female mice.

Restraint for 1 h induced significant antinociceptive activity, as assessed by the hot plate test, in female mice. The antinociceptive activity was significant throughout the 1 h period of observation starting immediately after restraint. Prior administration of the histamine H2 receptor agonist dimaprit (1.5-6.0 mg/kg s.c.) 15 min before restraint further enhanced the restraint-induced antinociceptive activity. Furthermore, the induction of antinociceptive activity by restraint was antagonised by prior administration of histamine H2 receptor antagonists, cimetidine (2.5-10.0 mg/kg s.c.) or zolantidine (2.5-10.0 mg/kg s.c.). However, when these drugs were administered immediately after restraint for 1 h, the antinociceptive activity observed was similar to those restrained animals receiving saline injection. The histamine receptor agonist and antagonists, at the doses used in the present study, did not affect the response of unrestrained animals to the hot plate test. These results demonstrate that the effect of a histamine H2 receptor agonist and antagonists on restraint-induced antinociception is dependent upon their time of administration and may act by altering the intensity of stress, thus affecting the antinociceptive activity induced.