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The Journal of Neuroscience, September 15, 2002, 22(18):8133-8138

FosB Regulates Wheel Running

Martin Werme¹, Chad Messer³, Lars Olson¹, Lauren Gilden³, Peter Thorén², Eric J. Nestler³, and Stefan Brené¹

Departments of ¹ Neuroscience and ² Physiology and Pharmacology, Karolinska Institutet, Stockholm, S-171 77 Sweden, and ³ Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070

FosB is a transcription factor that accumulates in a region-specific manner in the brain after chronic perturbations. For example, repeated administration of drugs of abuse increases levels of FosB in the striatum. In the present study, we analyzed the effect of spontaneous wheel running, as a model for a natural rewarding behavior, on levels of FosB in striatal regions. Moreover, mice that inducibly overexpress FosB in specific subpopulations of striatal neurons were used to study the possible role of FosB on running behavior. Lewis rats given ad libitum access to running wheels for 30 d covered what would correspond to ~10 km/d and showed increased levels of FosB in the nucleus accumbens compared with rats exposed to locked running wheels. Mice that overexpress FosB selectively in striatal dynorphin-containing neurons increased their daily running compared with control littermates, whereas mice that overexpress FosB predominantly in striatal enkephalin-containing neurons ran considerably less than controls. Data from the present study demonstrate that like drugs of abuse, voluntary running increases levels of FosB in brain reward pathways. Furthermore, overexpression of FosB in a distinct striatal output neuronal population increases running behavior. Because previous work has shown that FosB overexpression within this same neuronal population increases the rewarding properties of drugs of abuse, results of the present study suggest that FosB may play a key role in controlling both natural and drug-induced reward.

Key words: nucleus accumbens; striatum; locomotion; exercise; natural reward; behavioral addiction; compulsive; drugs of abuse

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22188133-06$05.00/0

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