The present study investigated the role of dopamine and the opioid system in the acquisition and maintenance of wheel running use (WR), employing D2L receptor-deficient (D2L-/-) mice as a model system. The daily administration of 1mg/kg of naloxone virtually abolished the acquisition of WR in D2L-/-, but did not modify the number of wheel turns after the consolidation of this behavior. These findings imply that both dopamine and opioid reward systems are necessary for WR consolidation, and they also suggest that reward systems in WR could vary according to the motivational stage of the animal.