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Serotonin neurons in the median raphe nucleus bidirectionally regulate somatic signs of nicotine withdrawal in mice

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Title: Serotonin neurons in the median raphe nucleus bidirectionally regulate somatic signs of nicotine withdrawal in mice
Authors: Nishitani, Naoya Browse this author
Ohmura, Yu Browse this author →KAKEN DB
Kobayashi, Keita Browse this author
Murashita, Taichi Browse this author
Yoshida, Takayuki Browse this author
Yoshioka, Mitsuhiro Browse this author →KAKEN DB
Keywords: Tobacco
Issue Date: 12-Jul-2021
Publisher: Elsevier
Journal Title: Biochemical and biophysical research communications
Volume: 562
Start Page: 62
End Page: 68
Publisher DOI: 10.1016/j.bbrc.2021.05.052
Abstract: In chronic smokers, nicotine withdrawal symptoms during tobacco cessation can lead to smoking relapse. In rodent models, chronic exposure to nicotine elicited physical dependence, whereas acute antagonism of nicotinic acetylcholine receptors (nAChRs) immediately precipitated withdrawal symptoms. Although the central serotonergic system plays an important role in nicotine withdrawal, the exact serotonergic raphe nuclei regulating these symptoms remain unknown. We used transgenic mice expressing archaerhodopsinTP009 or channelrhodopsin-2[C128S] exclusively in the central serotonergic neurons to selectively manipulate serotonergic neurons in each raphe nucleus. Nicotine withdrawal symptoms were precipitated by an acute injection of mecamylamine, a nonspecific nAChR antagonist, following chronic nicotine consumption. Somatic signs were used as measures of nicotine withdrawal symptoms. Acute mecamylamine administration significantly increased ptosis occurrence in nicotine drinking mice compared with that in control-drinking mice. Optogenetic inhibition of the serotonergic neurons in the median raphe nucleus (MRN), but not of those in the dorsal raphe nucleus (DRN), mimicked the symptoms observed during mecamylamine-precipitated nicotine withdrawal even in nicotine-na & iuml;ve mice following the administration of acute mecamylamine injection. Optogenetic activation of the serotonergic neurons in the MRN nearly abolished the occurrence of ptosis in nicotine drinking mice. The serotonergic neurons in the MRN, but not those in the DRN, are necessary for the occurrence of somatic signs, a nicotine withdrawal symptom, and the activation of these neurons may act as a potential therapeutic strategy for preventing the somatic manifestations of nicotine withdrawal. (c) 2021 Delhi Orthopedic Association. All rights reserved.
Rights: ©2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 大村 優

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