Inactivation pathway of histamine

根据Kasziba等人的报告，略微修改，构建了用于测量组胺和N^T-甲基组胺的HPLC系统。Hishida等人建立的高乙醇偏好（HAP）大鼠品系脑中组胺和N，N-甲基组胺的含量，组胺刺激HAP大鼠皮层时，PI的更新速率低于低乙醇偏好（low ethanol preference，HAP）大鼠，PI的更新速率低于低乙醇偏好（low ethanol preference，HAP）大鼠。甲基苯丙胺慢性处理小鼠的皮质PI周转率比对照小鼠小。这些结果表明，慢性乙醇或甲基苯丙胺处理后，组胺能神经元活性增强，组胺H_1受体-Gq/11-磷脂酶C信号转导通路下调，提示组胺能神经元系统在药物依赖中起重要作用，因此，研究了几种药物是否能改变甲基苯丙胺引起的运动增加、行为敏化和刻板行为。氯吉兰，A型单胺氧化酶抑制剂（MAOI），抑制甲基苯丙胺的过度运动和行为敏化。它延迟了刻板行为的发生，但这种影响不是剂量依赖性的。司来吉兰（一种B型单胺氧化酶抑制剂）对2-苯乙胺诱导的小鼠过度运动无影响，但能增加小鼠刻板行为。

An HPLC system for measurement of histamine and N^T-methylhistamine was constructed as reported by Kasziba et al. with slight modifications. The content of histamine and N^T-methylhistamine in the brain of the rat strain of high ethanol preference (HAP), established by Hishida et al., tended to be larger than those of the rat from low ethanol preference (LAP) strain.When the cortex of HAP was stimulated by histamine in vitro, turnover rate of phosphatidylinositols (PI) was lower than that of LAP. The cortex from mice chronically treated with methamphetamine showed smaller PI turnover rate than that of the control mice. These results suggested that after chronic ethanol or methamphetamine treamtment, activity of histaminergic neurons increases and signal transduction pathway through histamine H_1 receptor-Gq/11-phospholipase C was down-regulated.It was suggested that histaminergic neuron system plays important role in drug dependence, so several drugs were investigated if they can modify increased locomotion, behavioral sensitization, and stereotypic behavior induced by methamphetamine. Clorgyline, a type A monoamine oxidase inhibitor (MAOI), inhibited hyperlocomotion and behavioral sensitization by methamphetamine. It delayed the onset of stereotypic behavior but this effect was not dose-dependent. Selegiline (a type B MAOI) had no effect on hyperlocomotion but increased stereotypic behavior induced by 2-phenylethylamine.Knock-out vector of histamine N^T-methyltransferase was constructed and recombinant embryo was acquired.