Miyazaki S, Imaizumi M, Onodera K
Biology Laboratory, Yamasa Corporation, Choshi, Japan.
Methods Find Exp Clin Pharmacol. 1995 Nov;17 Suppl C:57-63.
We investigated the effects of histidine on scopolamine-induced learning deficits in the elevated plus-maze test in mice. In this test, transfer latency, the time mice took to move from the open arm to the enclosed arm, was used as an index of learning and memory. Intraperitoneal administration of scopolamine (0.5 mg/kg) prolonged the transfer latency on day 2 as compared with that in the saline-treated group. Histidine loading (500, 800 and 1600 mg/kg) reversed the prolongation of the transfer latency induced by scopolamine. This ameliorating effect of histidine was abolished by alpha-fluoromethylhistidine, an inhibitor of histidine decarboxylase, suggesting that histidine itself has no such ameliorating effect. Moreover, the ameliorating effect of histidine was antagonized by a histamine H1-receptor antagonist, pyrilamine, but not by zolantidine, a histamine H2-receptor antagonist. Thus, histamine, a decarboxylated product of histidine, elicited an ameliorating effect on scopolamine-induced learning deficit via histamine H1 receptors in mice. In the biochemical study, histidine significantly decreased acetylcholine (ACh) levels in the cerebral cortex and diencephalon of mice, and also significantly decreased them in the midbrain at a dose of 500 mg/kg. Histidine significantly increased and decreased levels of metabolites of noradrenaline and serotonin, respectively, in the brains of mice. Levels of dopamine and its metabolites were not very affected by histidine in the brains of mice. These findings clearly indicate that there is a close relationship between histaminergic and cholinergic system in the brain, and that histamine may play certain important roles in learning and memory.
我们在小鼠高架十字迷宫试验中研究了组氨酸对东莨菪碱诱导的学习缺陷的影响。在此试验中，转移潜伏期，即小鼠从开放臂移动到封闭臂所花费的时间，被用作学习和记忆的指标。与生理盐水处理组相比，腹腔注射东莨菪碱（0.5mg/kg）可使第2天的转移潜伏期延长。组氨酸负荷（500、800和1600mg/kg）可逆转东莨菪碱诱导的转移潜伏期延长。组氨酸脱羧酶抑制剂α-氟甲基组氨酸消除了组氨酸的这种改善作用，表明组氨酸本身没有这种改善作用。此外，组氨酸的改善作用被组胺H1受体拮抗剂吡苄明拮抗，但不被组胺H2受体拮抗剂佐兰丁拮抗。因此，组胺是组氨酸的脱羧产物，它通过小鼠体内的组胺H1受体对东莨菪碱诱导的学习缺陷产生改善作用。在生化研究中，组氨酸显著降低了小鼠大脑皮层和间脑中乙酰胆碱（ACh）的水平，并且在剂量为500mg/kg时也显著降低了中脑中ACh的水平。组氨酸分别显著增加和降低了小鼠脑中去甲肾上腺素和5-羟色胺代谢产物的水平。组氨酸对小鼠脑中多巴胺及其代谢产物的水平影响不大。这些发现清楚地表明，大脑中组胺能系统和胆碱能系统之间存在密切关系，并且组胺可能在学习和记忆中发挥某些重要作用。
