Wong J C
Neuropharmacology Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, United Kingdom.
Methods Find Exp Clin Pharmacol. 1999 Jul-Aug;21(6):403-7. doi: 10.1358/mf.1999.21.6.541920.
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.
在先前的研究中，已表明组胺会影响应激诱导的小鼠抗伤害感受活性。开展本研究是为了进一步探究组胺在此现象中的作用。通过热板试验评估发现，对雄性和雌性小鼠进行1小时的束缚均会诱导出显著的抗伤害感受活性。在束缚前15分钟预先皮下注射组胺H2受体激动剂二甲双咪（6.0毫克/千克）可增强抗伤害感受活性。此外，预先皮下注射组胺H2受体拮抗剂（10.0毫克/千克）西咪替丁或佐兰替丁可拮抗束缚诱导的抗伤害感受活性。在雄性小鼠中，在束缚前10分钟或束缚后立即皮下注射纳洛酮（4.0毫克/千克）并不影响束缚诱导的抗伤害感受。此外，二甲双咪的增强作用以及西咪替丁和佐兰替丁的抑制作用不受纳洛酮给药的影响。然而，在雌性小鼠中，束缚前10分钟给予纳洛酮可完全消除束缚诱导的抗伤害感受活性，且未观察到组胺H2受体激动剂和拮抗剂对束缚诱导的抗伤害感受的影响。此外，束缚后立即给予纳洛酮可减弱束缚诱导的抗伤害感受活性以及二甲双咪诱导的抗伤害感受活性增强作用。本研究结果进一步支持了我们之前的研究，即组胺H2受体很可能参与增强束缚诱导的抗伤害感受中的应激强度，从而改变所观察到的抗伤害感受程度。
