Further study on the effects of histamine H2 receptor agonist and antagonists on restraint-induced antinociception in mice.

In previous studies, histamine was shown to affect the antinociceptive activity induced by stress in mice. The present work was carried out to further examine the role of histamine in this phenomenon. Restraint for 1 h induced significant antinociceptive activity as assessed by the hot plate test in both male and female mice. The antinociceptive activity was enhanced by prior administration of the histamine H2 receptor agonist dimaprit (6.0 mg/kg s.c.) 15 min before restraint. Furthermore, the induction of antinociceptive activity by restraint was antagonized by prior administration of histamine H2 receptor antagonists (10.0 mg/kg s.c.), cimetidine or zolantidine. In the male mice, naloxone (4.0 mg/kg s.c.) administered 10 min before or immediately after restraint did not affect the antinociception induced by restraint. In addition, the potentiating effect of dimaprit and the inhibitory effect of cimetidine and zolantidine were not affected by administration of naloxone. However, in female mice, naloxone given 10 min before restraint completely abolished the induction of antinociceptive activity by restraint and the effects of histamine H2 receptor agonist and antagonists on restraint induced antinociception were not observed. Moreover, the antinociceptive activity induced by restraint and the dimaprit-induced potentiation of antinociceptive activity were diminished by naloxone administered immediately after the restraint. The present findings further support our previous studies which suggested that the histamine H2 receptor most probably is involved in enhancing the intensity of stress in restraint-induced antinociception thus altering the degree of antinociception observed.