TY - JOUR T1 - Behavioral Characterization of Mice Lacking Histamine H<sub>3</sub> Receptors JF - Molecular Pharmacology JO - Mol Pharmacol SP - 389 LP - 397 DO - 10.1124/mol.62.2.389 VL - 62 IS - 2 AU - Hiroshi Toyota AU - Christine Dugovic AU - Muriel Koehl AU - Aaron D. Laposky AU - China Weber AU - Karen Ngo AU - Ying Wu AU - Doo Hyun Lee AU - Kazuhiko Yanai AU - Eiko Sakurai AU - Takehiko Watanabe AU - Changlu Liu AU - Jingcai Chen AU - Ann J. Barbier AU - Fred W. Turek AU - Wai-Ping Fung-Leung AU - Timothy W. Lovenberg Y1 - 2002/08/01 UR - http://molpharm.aspetjournals.org/content/62/2/389.abstract N2 - 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. ER -