Behavioral characterization of mice lacking histamine H(3) receptors.
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.
Johnson & Johnson Pharmaceutical Research and Development, San Diego, California 92121, USA.
Hiroshi
H
Toyota
Christine
C
Dugovic
Muriel
M
Koehl
Aaron D
AD
Laposky
China
C
Weber
Karen
K
Ngo
Ying
Y
Wu
Doo Hyun
DH
Lee
Kazuhiko
K
Yanai
Eiko
E
Sakurai
Takehiko
T
Watanabe
Changlu
C
Liu
Jingcai
J
Chen
Ann J
AJ
Barbier
Fred W
FW
Turek
Wai-Ping
WP
Fung-Leung
Timothy W
TW
Lovenberg
D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000647:Amnesia / Q000139:chemically induced; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011869:Radioligand Assay; D018100:Receptors, Histamine H3 / Q000235:genetics / Q000502:physiology*; D012420:Running / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D000759:Adjuvants, Anesthesia; D015259:Dopamine Agents; D006633:Histamine Antagonists; D010880:Piperidines; D018100:Receptors, Histamine H3; D012701:Serotonin; D008694:Methamphetamine; D012601:Scopolamine; C052075:thioperamide; D004298:Dopamine; D009638:Norepinephrine