Behavioral characterization of mice lacking histamine H3 receptors

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

204 Scopus citations

Abstract

Brain histamine H3 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 H3 receptor in our laboratory has made it possible to create a transgenic line of mice devoid of H3 receptors. This paper provides the first description of the H3 receptor-deficient mouse (H3-/-), including molecular and pharmacologic, verification of the receptor deletion as well as phenotypic screens. The H3-/- mice showed a decrease in overall locomotion, wheel-running behavior, and body temperature during the dark phase but maintained normal circadian rhythmicity. H3-/- mice were insensitive to the wake-promoting effects of the H3 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 H3 receptor-deficient mouse represents a valuable model for studying histaminergic regulation of a variety of behaviors and neurotransmitter systems, including dopamine and acetylcholine.

Original languageEnglish (US)
Pages (from-to)389-397
Number of pages9
JournalMolecular pharmacology
Volume62
Issue number2
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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