Role of histamine H1-receptor on behavioral states and wake maintenance during deficiency of a brain activating system : A study using a knockout mouse model

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Parmentier , R , Zhao , Y , Perier , M , Akaoka , H , Lintunen , M , Hou , Y , Panula , P , Watanabe , T , Franco , P & Lin , J-S 2016 , ' Role of histamine H1-receptor on behavioral states and wake maintenance during deficiency of a brain activating system : A study using a knockout mouse model ' , Neuropharmacology , vol. 106 , pp. 20-34 . https://doi.org/10.1016/j.neuropharm.2015.12.014

Title: Role of histamine H1-receptor on behavioral states and wake maintenance during deficiency of a brain activating system : A study using a knockout mouse model
Author: Parmentier, Regis; Zhao, Yan; Perier, Magali; Akaoka, Hideo; Lintunen, Minnamaija; Hou, Yiping; Panula, Pertti; Watanabe, Takeshi; Franco, Patricia; Lin, Jian-Sheng
Contributor organization: Medicum
Pertti Panula / Principal Investigator
Neuroscience Center
Department of Anatomy
Date: 2016-07
Language: eng
Number of pages: 15
Belongs to series: Neuropharmacology
ISSN: 0028-3908
DOI: https://doi.org/10.1016/j.neuropharm.2015.12.014
URI: http://hdl.handle.net/10138/224098
Abstract: Using knockout (KO) mice lacking the histamine (HA)-synthesizing enzyme (histidine decarboxylase, HDC), we have previously shown the importance of histaminergic neurons in maintaining wakefulness (W) under behavioral challenges. Since the central actions of HA are mediated by several receptor subtypes, it remains to be determined which one(s) could be responsible for such a role. We have therefore compared the cortical-EEG, sleep and W under baseline conditions or behavioral/pharmacological stimuli in littermate wild-type (WT) and H1-receptor KO (H1-/-) mice. We found that H1-/- mice shared several characteristics with HDC KO mice, i.e. 1) a decrease in W after lights-off despite its normal baseline daily amount; 2) a decreased EEG slow wave sleep (SWS)/W power ratio; 3) inability to maintain W in response to behavioral challenges demonstrated by a decreased sleep latency when facing various stimuli. These effects were mediated by central H1-receptors. Indeed, in WT mice, injection of triprolidine, a brain-penetrating H1-receptor antagonist increased SWS, whereas ciproxifan (H3-receptor antagonist/inverse agonist) elicited W; all these injections had no effect in H1-/- mice. Finally, H1-/- mice showed markedly greater changes in EEG power (notably in the 0.8-5 Hz band) and sleep-wake cycle than in WT mice after application of a cholinergic antagonist or an indirect agonist, i.e., scopolamine or physostigmine. Hence, the role of HA in wake-promotion is largely ensured by H1-receptors. An upregulated cholinergic system may account for a quasi-normal daily amount of W in HDC or H1-receptor KO mice and likely constitutes a major compensatory mechanism when the brain is facing deficiency of an activating system. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright (C) 2015 Elsevier Ltd. All rights reserved.
Subject: Wakefulness
Arousal
Sleep
Cortical activation
Histamine
H1-receptor
Knockout mice
EEG
Behavior
Cholinergic transmission
Compensation
SLEEP-WAKING CYCLE
OUT MICE
POSTERIOR HYPOTHALAMUS
PARADOXICAL SLEEP
CEREBRAL-CORTEX
NERVOUS-SYSTEM
NEURONS
WAKEFULNESS
RECEPTORS
ANTAGONISTS
3112 Neurosciences
3111 Biomedicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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