MISC

2007年4月

Pleiotropic impact of constitutive fosB inactivation on nicotine-induced behavioral alterations and stress-related traits in mice

HUMAN MOLECULAR GENETICS
  • Hongwen Zhu
  • ,
  • MoonSook Lee
  • ,
  • Soh Agatsuma
  • ,
  • Noboru Hiroi

16
7
開始ページ
820
終了ページ
836
記述言語
英語
掲載種別
書評論文,書評,文献紹介等
DOI
10.1093/hmg/ddm027
出版者・発行元
OXFORD UNIV PRESS

Multiple genes are thought to influence both susceptibility to nicotine dependence and its comorbid behavioral traits in humans. However, which specific genes contribute to this pleiotropic effect is poorly understood. Previous rodent studies have shown that many addictive substances and stressful stimuli increase the expression of the transcription factor FosB in limbic and associated regions and that the protein products of fosB contribute to certain behavioral effects of cocaine and morphine. However, the role of this gene in nicotine-regulated behaviors and dependence-related behavioral traits is unknown. We tested the hypothesis that a constitutive level of FosB affects nicotine-regulated behaviors and comorbid behavioral traits using constitutive fosB knockout (KO) mice. Following repeated or prolonged nicotine administration, but not a single acute administration, KO mice were impaired in conditioned place preference, oral nicotine intake and motor suppression. In wild-type mice, repeated nicotine injections, but not a single acute injection, increased the expression of FosB and its truncated variant Delta FosB in the targets but not at the origins of the mesolimbic and nigrostriatal dopamine pathways; no detectable level of FosB/Delta FosB was found in KO mice. In tasks designed to assess behavioral traits, KO mice exhibited more pronounced behavioral abnormalities when stress levels were high than when they were minimized. Our results suggest that the constitutive absence of fosB has a pleiotropic influence on the behavioral effects of repeated or prolonged nicotine administration and on stress-related behavioral traits in mice.

リンク情報
DOI
https://doi.org/10.1093/hmg/ddm027
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000246122400010&DestApp=WOS_CPL
ID情報
  • DOI : 10.1093/hmg/ddm027
  • ISSN : 0964-6906
  • Web of Science ID : WOS:000246122400010

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