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The Journal of Neuroscience, September 6, 2006, 26(36):9196-9204; doi:10.1523/JNEUROSCI.1124-06.2006

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Behavioral/Systems/Cognitive
FosB in the Nucleus Accumbens Regulates Food-Reinforced Instrumental Behavior and Motivation

Peter Olausson,¹ J. David Jentsch,² Natalie Tronson,¹ Rachel L. Neve,³ Eric J. Nestler,⁴ and Jane R. Taylor¹

¹Department of Psychiatry, Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508, ²Department of Psychology, University of California, Los Angeles, California 90095, ³Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02178, and ⁴Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas 75390

Correspondence should be addressed to Jane R. Taylor, Department of Psychiatry, Division of Molecular Psychiatry, Yale University School of Medicine, Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508. Email: jane.taylor{at}yale.edu

Alterations in motivation have been implicated in the pathophysiology of several psychiatric disorders, including substance abuse and depression. Repeated exposure to drugs of abuse or stress is known to persistently induce the transcription factor FosB in the nucleus accumbens (NAc) and dorsal striatum, effects hypothesized to contribute to neuroadaptations in dopamine-regulated signaling. Little is known, however, about the specific involvement of FosB in dysregulation of appetitively motivated behaviors. We show here that inducible overexpression of FosB in NAc and dorsal striatum of bitransgenic mice, or specifically in the NAc core of rats by use of viral-mediated gene transfer, enhanced food-reinforced instrumental performance and progressive ratio responding. Very similar behavioral effects were found after previous repeated exposure to cocaine, amphetamine, MDMA [(+)-3,4-methylenedioxymethamphetamine], or nicotine in rats. These results reveal the powerful regulation of motivational processes by FosB, and provide evidence that drug-induced alterations in gene expression via induction of FosB within the NAc core may play a critical role in the impact of motivational influences on instrumental behavior.

Key words: addiction; psychostimulant; reinforcement; dopamine; gene expression; transcription factors

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Received March 15, 2006; revised June 23, 2006; accepted Aug. 2, 2006.

Correspondence should be addressed to Jane R. Taylor, Department of Psychiatry, Division of Molecular Psychiatry, Yale University School of Medicine, Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508. Email: jane.taylor{at}yale.edu

Related articles in J. Neurosci.:

FosB: A Molecular Gate to Motivational Processes within the Nucleus Accumbens?

David Belin and Aude Rauscent
J. Neurosci. 2006 26: 11809-11810. [Full Text]  

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