ΔFosB regulates wheel running

ΔFosB 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 ΔFosB 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 ΔFosB in striatal regions. Moreover, mice that inducibly overexpress ΔFosB in specific subpopulations of striatal neurons were used to study the possible role of ΔFosB 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 ΔFosB in the nucleus accumbens compared with rats exposed to locked running wheels. Mice that overexpress ΔFosB selectively in striatal dynorphin-containing neurons increased their daily running compared with control littermates, whereas mice that overexpress ΔFosB 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 ΔFosB in brain reward pathways. Furthermore, overexpression of ΔFosB in a distinct striatal output neuronal population increases running behavior. Because previous work has shown that ΔFosB overexpression within this same neuronal population increases the rewarding properties of drugs of abuse, results of the present study suggest that ΔFosB may play a key role in controlling both natural and drug-induced reward.