Miyazaki S, Imaizumi M, Onodera K
Biology Laboratory, Research & Development Division, Yamasa Corporation, Choshi, Chiba.
Methods Find Exp Clin Pharmacol. 1995 Dec;17(10):653-8.
We investigated the effects of thioperamide, a histamine H3-receptor antagonist, on a scopolamine-induced learning deficit in the step-through passive avoidance test in mice, and on contents of acetylcholine and choline in the brain. In a behavioral study, thioperamide (20 mg/kg) alone slightly ameliorated scopolamine-induced learning deficit, and pretreatment with zolantidine, a histamine H2-receptor antagonist, significantly enhanced the ameliorating effect of thioperamide. This enhanced ameliorating effect of thioperamide was antagonized by pyrilamine, a histamine H1-receptor antagonist and (R)-alpha-methylhistamine, a histamine H3-receptor agonist, suggesting that thioperamide showed the ameliorating effect via histamine H3 receptors and/or histamine H1 receptors. In the biochemical study, thioperamide (20 mg/kg) in combination with zolantidine (20 mg/kg) significantly increased contents of choline in most of brain regions. These findings suggest that there is a close relationship between histaminergic and cholinergic systems in the brain, and that the histaminergic system may play certain important roles in learning and memory.
我们研究了组胺H3受体拮抗剂硫代哌酰胺对东莨菪碱诱导的小鼠被动回避试验学习缺陷以及对大脑中乙酰胆碱和胆碱含量的影响。在行为学研究中，单独使用硫代哌酰胺（20 mg/kg）可轻微改善东莨菪碱诱导的学习缺陷，而组胺H2受体拮抗剂佐兰替丁预处理可显著增强硫代哌酰胺的改善作用。组胺H1受体拮抗剂吡苄明和组胺H3受体激动剂（R）-α-甲基组胺可拮抗硫代哌酰胺这种增强的改善作用，提示硫代哌酰胺通过组胺H3受体和/或组胺H1受体发挥改善作用。在生化研究中，硫代哌酰胺（20 mg/kg）与佐兰替丁（20 mg/kg）联合使用可显著增加大多数脑区的胆碱含量。这些发现表明，大脑中组胺能系统与胆碱能系统之间存在密切关系，且组胺能系统可能在学习和记忆中发挥某些重要作用。
