Inactivation pathway of histamine

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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.