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Histidine decarboxylase (HDC) synthesizes histamine from histidine in mammals. To evaluate the role of histamine, we generated HDC-deficient mice using a gene targeting method. The mice showed a histamine deficiency and lacked histamine-synthesizing activity from histidine. These HDC-deficient mice are viable and fertile but exhibit a decrease in the(More)
The effect of clobenpropit (VUF-9153), a new histamine H3 receptor antagonist, on electrically induced convulsions was studied in mice. Clobenpropit significantly and dose dependently decreased the duration of each convulsive phase. Its anticonvulsant effects were prevented by pretreatment with (R)-alpha-methylhistamine and imetit (VUF-8325), histamine H3(More)
A growing amount of evidence suggests that a deficiency in hypocretin/orexin neurotransmission is critically involved in animal and human forms of narcolepsy. Since hypocretin-containing neurons innervate and excite histaminergic tuberomammillary neurons, altered histaminergic neurotransmission may also be involved in narcolepsy. We found a significant(More)
Behavioural assessments were made of mutant mice lacking histamine H1 receptors to reveal the function of H1 receptors in the behaviour of mice. Exploratory behaviour of mice in a new environment was examined to discover whether the absence of H1 receptors in mice affects actions relating to their emotions. The H1 receptor-deficient mice showed a(More)
In this study, we examined the changes in neuronal histamine (HA) release in the rat striatum after acute and repeated administration of methamphetamine (METH). We studied the regulation of METH-induced HA release by dopamine receptors and the relationship between METH-induced HA release and stereotyped behavior. Acute administration of METH (1 mg/kg)(More)
We have recently suggested that the brain histamine has an inhibitory role on the behavioral effects of methamphetamine by pharmacological studies. In this study, we used the histidine decarboxylase gene knockout mice and measured the spontaneous locomotor activity, the changes of locomotion by single and repeated administrations of methamphetamine, and the(More)
To examine biochemical changes in the brain histamine (HA) neuron system after acute and chronic administrations of methamphetamine (MAP), HA levels and histidine decarboxylase (HDC) activities in the rat cortex, striatum, diencephalon, midbrain, pons-medulla and cerebellum were measured. In the cortex and striatum, acute administration of MAP (1 and 3(More)
The purpose of this study was to further investigate the effects of chlorpheniramine (d- and dl-forms) on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the regional parts of rat brain. After the intravenous administration of each form of chlorpheniramine, the 5-HT and 5-HIAA levels were measured by HPLC system. Each form of(More)
The transport characteristics of l- and d-histidine through the blood-brain barrier (BBB) were studied using cultured rat brain microvascular endothelial cells (BMEC). l-Histidine uptake was a saturable process. A decrease in incubation temperature from 37 to 0 degreesC or the addition of metabolic inhibitors (DNP and rotenone) reduced the uptake rate of(More)
The postnatal ontogenetic development of the histamine receptor subtypes was studied in rat brain by quantitative receptor autoradiography with highly sensitive imaging plates. H1 receptor binding sites labeled with [3H]pyrilamine were detected on postnatal day 2 (P2) and increased very slowly until P9, and then rapidly reaching the adult levels in the(More)