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Birkhuser Verlag, Basel, 2008
Inamm. res. 57, Supplement 1 (2008) S39S401023-3830/08/01S39-02DOI 10.1007/s00011-007-0620-4 Inammation Research
The roles of histamine H1 receptors on cognition
K. Yanai, H. Dai, E. Sakurai and T. Watanabe
Department of Pharmacology, Tohoku University School of Medicine, Sendai 980-8575, Japan, Fax:++81 227178060, e-mail: [email protected]
Published Online First 14 March 2008
Introduction
Histamine neurons are located exclusively in the posterior hypothalamus, from where they project diffusely to all regions of brain. Neuronal histamine has been implicated in a variety of brain functions including wakefulness, learning and memory [1]. Although it is well known that sedative antihistamines induce cognitive decline in humans through blockage of H1 receptor [2], both facilitatory and inhibitory effects of neuronal histamine on learning and memory have been described in animal behavioral studies [3, 4]. Histaminergic neurotransmission has been also implicated in pathophysiology of stress-related psychiatric diseases [5]. Although several atypical antipsychotics are potent H1 antagonists [6], the clinical signicance of interaction between atypical antipsychotics and H1 receptors is still unknown. The aim of this study was to investigate the role of histamine H1 receptors on cognition in normal conditions using H1 receptor gene knockout mice (H1KO). We also investigated the effects of H1 receptor blockade on social isolation-induced behavioral and neurochemical changes in H1KO mice and their wild-type (WT) mice.
Materials and methods
Experiment 1: Under socially-reared normal conditions, learning and memory were evaluated in H1KO mice by object recognition, Barnes maze and fear conditioning tests. These behavioral tasks are dependent on the function of prefrontal cortex, hippocampus or amygdala. Furthermore, we also examined long-term potentiation (LTP) in CA1 area of hippocampus in H1KO mice and their WT mice.
Experiment 2: H1KO and WT mice were subjected to social isolation immediately after weaning. After 4-week social isolation, locomotion, pre-pulse inhibition (PPI) of startle...