Behavioral Characterization of Mice Lacking Histamine H3 Receptors

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 me...

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Published inMolecular pharmacology Vol. 62; no. 2; p. 389
Main Authors Hiroshi Toyota, Christine Dugovic, Muriel Koehl, Aaron D. Laposky, China Weber, Karen Ngo, Ying Wu, Doo Hyun Lee, Kazuhiko Yanai, Eiko Sakurai, Takehiko Watanabe, Changlu Liu, Jingcai Chen, Ann J. Barbier, Fred W. Turek, Wai-Ping Fung-Leung, Timothy W. Lovenberg
Format Journal Article
LanguageEnglish
Japanese
Published American Society for Pharmacology and Experimental Therapeutics 01.08.2002
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Abstract 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.
AbstractList 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.
Author Ann J. Barbier
Ying Wu
Timothy W. Lovenberg
Jingcai Chen
Karen Ngo
Muriel Koehl
Takehiko Watanabe
China Weber
Kazuhiko Yanai
Eiko Sakurai
Christine Dugovic
Hiroshi Toyota
Doo Hyun Lee
Aaron D. Laposky
Changlu Liu
Wai-Ping Fung-Leung
Fred W. Turek
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