Skip Navigation

Human Molecular Genetics 2007 16(7):820-836; doi:10.1093/hmg/ddm027
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow Supplementary Data
Right arrow Supplementary Data
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (6)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Zhu, H.
Right arrow Articles by Hiroi, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhu, H.
Right arrow Articles by Hiroi, N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Hongwen Zhu1,2, MoonSook Lee1, Soh Agatsuma1 and Noboru Hiroi1,2,*

1 Laboratory of Molecular Psychobiology, Department of Psychiatry and Behavioral Sciences and 2 Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA

* To whom correspondence should be addressed at: Laboratory of Molecular Psychobiology, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Tel: +1 7184303124; Fax: +1 7184303125; Email: hiroi{at}aecom.yu.edu

Received January 9, 2007; Accepted February 4, 2007

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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
G. Suzuki, K. M. Harper, T. Hiramoto, B. Funke, M. Lee, G. Kang, M. Buell, M. A. Geyer, R. Kucherlapati, B. Morrow, et al.
Over-expression of a human chromosome 22q11.2 segment including TXNRD2, COMT and ARVCF developmentally affects incentive learning and working memory in mice
Hum. Mol. Genet., October 15, 2009; 18(20): 3914 - 3925.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
G. Suzuki, K. M. Harper, T. Hiramoto, T. Sawamura, M. Lee, G. Kang, K. Tanigaki, M. Buell, M. A. Geyer, W. S. Trimble, et al.
Sept5 deficiency exerts pleiotropic influence on affective behaviors and cognitive functions in mice
Hum. Mol. Genet., May 1, 2009; 18(9): 1652 - 1660.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.