Δ<i>FosB</i>Regulates Wheel Running

Abstract

Δ<i>FosB</i> 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 Δ<i>FosB</i> 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 Δ<i>FosB</i> in striatal regions. Moreover, mice that inducibly overexpress Δ<i>FosB</i>in specific subpopulations of striatal neurons were used to study the possible role of Δ<i>FosB</i> on running behavior. Lewis rats given <i>ad libitum</i> access to running wheels for 30 d covered what would correspond to ∼10 km/d and showed increased levels of Δ<i>FosB</i> in the nucleus accumbens compared with rats exposed to locked running wheels. Mice that overexpress Δ<i>FosB</i> selectively in striatal dynorphin-containing neurons increased their daily running compared with control littermates, whereas mice that overexpress Δ<i>FosB</i> 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 Δ<i>FosB</i> in brain reward pathways. Furthermore, overexpression of Δ<i>FosB</i> in a distinct striatal output neuronal population increases running behavior. Because previous work has shown that Δ<i>FosB</i> overexpression within this same neuronal population increases the rewarding properties of drugs of abuse, results of the present study suggest that Δ<i>FosB</i> may play a key role in controlling both natural and drug-induced reward.