Impaired locomotor activity and exploratory behavior in mice lacking histamine H1 receptors

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 23; pp. 13316 - 13320
• Main Authors: Inoue, I, Yanai, K, Kitamura, D, Taniuchi, I, Kobayashi, T, Niimura, K, Watanabe, T
• Format: Journal Article
• Language: English
• Published: United States National Acad Sciences 12.11.1996; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Animals; Base Sequence; Biological Sciences; Brain - metabolism; Brain - physiology; Circadian Rhythm; Darkness; DNA Primers; Doxepin - metabolism; Exploratory Behavior; Genomic Library; Heterozygote; Homozygote; Light; Mice; Mice, Knockout; Mice, Neurologic Mutants; Motor Activity; Neurology; Neurons; Polymerase Chain Reaction; Pyrilamine - metabolism; Receptors, Histamine H1 - genetics; Receptors, Histamine H1 - metabolism; Reference Values; Restriction Mapping; Rodents
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.23.13316

From pharmacological studies using histamine antagonists and agonists, it has been demonstrated that histamine modulates many physiological functions of the hypothalamus, such as arousal state, locomotor activity, feeding, and drinking. Three kinds of receptors (H 1 , H 2 , and H 3 ) mediate these actions. To define the contribution of the histamine H 1 receptors (H1R) to behavior, mutant mice lacking the H1R were generated by homologous recombination. In brains of homozygous mutant mice, no specific binding of [ 3 H]pyrilamine was seen. [ 3 H]Doxepin has two saturable binding sites with higher and lower affinities in brains of wild-type mice, but H1R-deficient mice showed only the weak labeling of [ 3 H]doxepin that corresponds to lower-affinity binding sites. Mutant mice develop normally, but absence of H1R significantly increased the ratio of ambulation during the light period to the total ambulation for 24 hr in an accustomed environment. In addition, mutant mice significantly reduced exploratory behavior of ambulation and rearings in a new environment. These results indicate that through H1R, histamine is involved in circadian rhythm of locomotor activity and exploratory behavior as a neurotransmitter.