Impaired locomotor activity and exploratory behavior in mice lacking histamine H-1 receptors
Impaired locomotor activity and exploratory behavior in mice lacking histamine H-1 receptors
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DOI：
10.1073/pnas.93.23.13316
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发表时间：
1996-11-12
影响因子：
11.1
通讯作者：
Watanabe, T
中科院分区：
文献类型：
--
作者：
Inoue, I;Yanai, K;Watanabe, T
从使用组胺拮抗剂和激动剂的药理学研究中，已经证明组胺调节下丘脑的许多生理功能，如觉醒状态，运动活动，进食和饮水，三种受体（H-1， H-2和H-3）介导这些作用，为了确定组胺H-1受体（H1R）对行为的贡献，通过同源重组产生缺乏H1R的突变小鼠，在纯合突变小鼠的大脑中，未观察到[(3)]吡咯胺的特异性结合。[H-3]Doxepin在野生型小鼠的大脑中有两个亲和性较高和较低的饱和结合位点，而H1R缺失小鼠仅表现出与低亲和性结合位点相对应的[H-3]Doxepin的弱标记，突变小鼠发育正常，但在习惯的环境中，缺乏H1R显著增加了光照期活动占总活动的比例。这些结果表明，通过H1R，组胺作为一种神经递质参与了运动活动的昼夜节律和探索行为。
From pharmacological studies using histamine antagonists and agonists, it has been demonstrated that histamine modulates many physiological functions of the hypothalamus, such as arousal state, locomotor activity, feeding, and drinking, Three kinds of receptors (H-1, H-2, and H-3) mediate these actions, To define the contribution of the histamine H-1 receptors (H1R) to behavior, mutant mice lacking the H1R were generated by homologous recombination, In brains of homozygous mutant mice, no specific binding of [(3)]pyrilamine was seen. [H-3]Doxepin has two saturable binding sites with higher and lower affinities in brains of wild-type mice, but H1R-deficient mice showed only the weak labeling of [H-3]doxepin that corresponds to lower-affinity binding sites, Mutant mice develop normally, but absence of H1R significantly increased the ratio of ambulation during the light period to the total ambulation for 24 hr in an accustomed environment, In addition, mutant mice significantly reduced exploratory behavior of ambulation and rearings in a nem environment, These results indicate that through H1R, histamine is involved in circadian rhythm of locomotor activity and exploratory behavior as a neurotransmitter.