title: Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors.
abstract: Previous pharmacological experiments provide conflicting findings that describe both facilitatory and inhibitory effects of neuronal histamine on learning and memory. Here, we examined learning and memory and synaptic plasticity in mice with a null mutation of gene coding histamine H1 or H2 receptor in order to clarify the role of these receptors in learning and memory processes. Learning and memory were evaluated by several behavioral tasks including object recognition, Barnes maze and fear conditioning. These behavioral tasks are highly dependent on the function of prefrontal cortex, hippocampus or amygdala. Object recognition and Barnes maze performance were significantly impaired in both H1 receptor gene knockout (H1KO) and H2 receptor gene knockout (H2KO) mice when compared to the respective wild-type (WT) mice. Conversely, both H1KO and H2KO mice showed better auditory and contextual freezing acquisition than their respective WT mice. Furthermore, we also examined long-term potentiation (LTP) in the CA1 area of hippocampus in H1KO and H2KO mice and their respective WT mice. LTP in the CA1 area of hippocampus was significantly reduced in both H1KO and H2KO mice when compared with their respective WT mice. In conclusion, our results demonstrate that both H1 and H2 receptors are involved in learning and memory processes for which the frontal cortex, amygdala and hippocampus interact.
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, 2-1 Seiryo-Machi, Sendai, Japan.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Dai
authors.forename: Kenya
authors.initials: K
authors.lastname: Kaneko
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kato
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Jing
authors.forename: Ajing
authors.initials: A
authors.lastname: Xu
authors.forename: Eiko
authors.initials: E
authors.lastname: Sakurai
authors.forename: Motohisa
authors.initials: M
authors.lastname: Kato
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kuramasu
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003072:Cognition Disorders / Q000235:genetics* / Q000473:pathology; D003213:Conditioning, Psychological / Q000502:physiology; D005239:Fear; D006624:Hippocampus / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000235:genetics; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009483:Neuropsychological Tests; D011969:Receptors, Histamine H1 / Q000172:deficiency*; D011970:Receptors, Histamine H2 / Q000172:deficiency*
chemical_list: D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2