First Author | Toyota H | Year | 2002 |
Journal | Mol Pharmacol | Volume | 62 |
Issue | 2 | Pages | 389-97 |
PubMed ID | 12130692 | Mgi Jnum | J:79168 |
Mgi Id | MGI:2387355 | Doi | 10.1124/mol.62.2.389 |
Citation | Toyota H, et al. (2002) Behavioral characterization of mice lacking histamine H(3) receptors. Mol Pharmacol 62(2):389-97 |
abstractText | 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. |