RT Journal Article SR Electronic T1 Behavioral Characterization of Mice Lacking Histamine H3 Receptors JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 389 OP 397 DO 10.1124/mol.62.2.389 VO 62 IS 2 A1 Hiroshi Toyota A1 Christine Dugovic A1 Muriel Koehl A1 Aaron D. Laposky A1 China Weber A1 Karen Ngo A1 Ying Wu A1 Doo Hyun Lee A1 Kazuhiko Yanai A1 Eiko Sakurai A1 Takehiko Watanabe A1 Changlu Liu A1 Jingcai Chen A1 Ann J. Barbier A1 Fred W. Turek A1 Wai-Ping Fung-Leung A1 Timothy W. Lovenberg YR 2002 UL http://molpharm.aspetjournals.org/content/62/2/389.abstract AB 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 H3receptor-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 H3receptor-deficient mouse represents a valuable model for studying histaminergic regulation of a variety of behaviors and neurotransmitter systems, including dopamine and acetylcholine.