著者

Masaaki Tagawa Michiko Kano Nobuyuki Okamura Masatoshi Itoh Eiko Sakurai Takehiko Watanabe Kazuhiko Yanai

出版者

The Japanese Pharmacological Society

雑誌

The Japanese Journal of Pharmacology (ISSN:00215198)

巻号頁・発行日

vol.83, no.3, pp.253-260, 2000 (Released:2001-01-31)

参考文献数

46

被引用文献数

16 14

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Ethanol is a social drug and has been generally known to be a CNS depressant.A large fluctuation of blood alcohol concentration(BAC)is well−known to occur due to main factors such as the genetic polymorphism of the main alcohol metabolizing enzymes and the effect of blood.Few studies have substantially discussed the relationship between impaired CNS activities and BAC.In this study, focusing on the correlation of BAC, we investigated the acute effects of alcohol intake on cognitive performance in humans by objective evaluation methods consisting of the attention−demanding cognitive tasks.Tasks were administered to ten healthy male volunteers before and after ingesting established amounts of alcohol.With increased BAC, we observed prolongation of reaction time performances and lowering of a coordination performance.From the results, we concluded that cognitive performance deteriorates with an increase of BAC.Additionally, the BAC threshold that causes significant impairment of cognitive performance was estimated to be approximately 50 mg/dl(ca.10 mM).

著者

Tomohiro Okuda Dongying Zhang He Shao Nobuyuki Okamura Naoko Takino Tatsunori Iwamura Eiko Sakurai Takeo Yoshikawa Kazuhiko Yanai

出版者

The Japanese Pharmacological Society

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.111, no.2, pp.167-174, 2009 (Released:2009-10-15)

参考文献数

26

被引用文献数

17 27

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Histamine H3 receptors inhibit the release of not only histamine itself, but also other neurotransmitters including dopamine. Previous papers have reported that histaminergic neurons inhibit psychostimulant-induced behavioral changes. To examine whether deficiency in histamine H3 receptors influences psychostimulant-induced behavioral sensitization and reward, we examined locomotor activity, conditioned place preference (CPP), and c-Fos expression in histamine H3 receptor–gene knockout mice (H3KO) and their wild-type (WT) counterparts before and after treatment with methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA). The increase in locomotion induced by treatment with METH or MDMA was lower in histamine H3KO mice than in WT mice, while the locomotor sensitization was developed by METH or MDMA in both strains. However, no significant difference in METH- and MDMA-induced preference scores of CPP between histamine H3KO mice and WT mice was observed. Following treatment with METH, the number of c-Fos–positive neurons in the the caudate-putamen of histamine H3KO mice was lower than that in the caudate-putamen of WT mice. In contrast, there was no significant difference in the number of the psychostimulant-induced c-Fos–positive cells in the nucleus accumbens between the two strains of mice. These findings suggest that deficiency in histamine H3 receptors may have inhibitory effects on psychostimulant-induced increase in locomotion, but insignificant effects on the reward.

著者

Nobuyuki Okamura Hidetoshi Miyauchi Tominari Choshi Takashi Ishizu Akira Yagi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.5, pp.658-661, 2003 (Released:2003-05-01)

参考文献数

19

被引用文献数

7 9

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A method for semi-micro high-performance liquid chromatography (HPLC) has been established for the simultaneous determination of 3α-hydroxyglycyrrhetic acid and 3-dehydroglycyrrhetic acid together with glycyrrhizin, glycyrrhetic acid and glycyrrhetic acid mono-glucuronide formed by incubation of glycyrrhizin with rat feces. The analysis was accomplished within 25 min with a TSKgel ODS-80TsQA (150×2.0 mm i.d.) column by linear gradient elution using a mobile phase containing aqueous phosphoric acid and acetonitrile at a flow rate of 0.2 ml·min−1, a thermostatic oven at 25 °C, and detection at 254 nm. The detection limits of these compounds were 0.2 pmol per injection (5 μl). The metabolites of glycyrrhizin, by anaerobic or aerobic incubation with rat fecal suspension over 48 h, were determined. Glycyrrhizin was almost completely converted to metabolite glycyrrhetic acid, and metabolites 3α-hydroxyglycyrrhetic acid and 3-dehydroglycyrrhetic acid in negligible amounts in anaerobic conditions. However, the metabolic time courses of 3-dehydroglycyrrhetic acid when incubated in aerobic conditions revealed that it apparently continued increasing during the whole incubation period.