Behavioral characterization of mice lacking histamine H(3) receptors.

Behavioral characterization of mice lacking histamine H(3) receptors.
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DOI:
10.1124/mol.62.2.389
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发表时间:
2002-08
影响因子:
3.6
通讯作者:
H. Toyota;C. Dugovic;M. Koehl;A. Laposky;C. Weber;K. Ngo;Ying Wu;D. H. Lee;K. Yanai;E. Sakurai;Takehiko Watanabe;Changlu Liu;Jingcai Chen;A. Barbier;F. Turek;W. Fung-Leung;T. Lovenberg
H. Toyota;C. Dugovic;M. Koehl;A. Laposky;C. Weber;K. Ngo;Ying Wu;D. H. Lee;K. Yanai;E. Sakurai;Takehiko Watanabe;Changlu Liu;Jingcai Chen;A. Barbier;F. Turek;W. Fung-Leung;T. Lovenberg
中科院分区:
医学3区
文献类型:
--
作者:
H. Toyota;C. Dugovic;M. Koehl;A. Laposky;C. Weber;K. Ngo;Ying Wu;D. H. Lee;K. Yanai;E. Sakurai;Takehiko Watanabe;Changlu Liu;Jingcai Chen;A. Barbier;F. Turek;W. Fung-Leung;T. Lovenberg

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Brain histamine H(3) receptors are predominantly presynaptic and serve an important autoregulatory function for the release of histamine and other neurotransmitters. They have been implicated in a variety of brain functions, including arousal, locomotor activity, thermoregulation, food intake, and memory. The recent cloning of the H(3) receptor in our laboratory has made it possible to create a transgenic line of mice devoid of H(3) receptors. This paper provides the first description of the H(3) receptor-deficient mouse (H(3)(-/-)), including molecular and pharmacologic verification of the receptor deletion as well as phenotypic screens. The H(3)(-/-) mice showed a decrease in overall locomotion, wheel-running behavior, and body temperature during the dark phase but maintained normal circadian rhythmicity. H(3)(-/-) mice were insensitive to the wake-promoting effects of the H(3) receptor antagonist thioperamide. We also observed a slightly decreased stereotypic response to the dopamine releaser, methamphetamine, and an insensitivity to the amnesic effects of the cholinergic receptor antagonist, scopolamine. These data indicate that the H(3) receptor-deficient mouse represents a valuable model for studying histaminergic regulation of a variety of behaviors and neurotransmitter systems, including dopamine and acetylcholine.