title: Fasting activated histaminergic neurons and enhanced arousal effect of caffeine in mice.
abstract: Caffeine, a popular psychoactive compound, promotes wakefulness via blocking adenosine A2A receptors in the shell of the nucleus accumbens, which projects to the arousal histaminergic tuberomammillary nucleus (TMN). The TMN controls several behaviors such as wakefulness and feeding. Fasting has been reported to activate the TMN histaminergic neurons to increase arousal. Therefore, we propose that caffeine may promote greater arousal under fasting rather than normal feeding conditions. In the current study, locomotor activity recording, electroencephalogram (EEG) and electromyogram recording and c-Fos expression were used in wild type (WT) and histamine H1 receptor (H1R) knockout (KO) mice to investigate the arousal effects of caffeine under fasting conditions. Caffeine (15mg/kg) enhanced locomotor activity in fasted mice for 5h, but only did so for 3h in normally fed animals. Pretreatment with the H1R antagonist pyrilamine abolished caffeine-induced stimulation on locomotor activity in fasted mice. EEG recordings confirmed that caffeine-induced wakefulness for 3h in fed WT mice, and for 5h in fasted ones. A stimulatory effect of caffeine was not observed in fasted H1R KO mice. Furthermore, c-Fos expression was increased in the TMN under fasting conditions. These results indicate that caffeine had greater wakefulness-promoting effects in fasted mice through the mediation of H1R.
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China. Electronic address: yiqunwang@fudan.edu.cn.
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China; Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Zhu
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Ibaraki, Japan.
authors.forename: Yohko
authors.initials: Y
authors.lastname: Takata
authors.affiliation: The Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Meng-Qi
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: li.shanqun@zs-hospital.sh.cn.
authors.forename: Shan-Qun
authors.initials: SQ
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, Shanghai, China; The Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: quweimin@fudan.edu.cn.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Qu
mesh_terms: D000818:Animals; D001143:Arousal / Q000187:drug effects*; D002110:Caffeine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005215:Fasting / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011738:Pyrilamine / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
chemical_list: D006634:Histamine H1 Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011969:Receptors, Histamine H1; D002110:Caffeine; D011738:Pyrilamine
keywords: Caffeine; EEG; Fasted; H(1)R; Wakefulness