In this presentation, we hypothesized that μ-opioid receptor antagonists could inhibit the natural reward as well as drug addiction such as opioids and stimulants. To evaluate natural reward, horizontal running wheels were applied to mice administered with a μ-opioid receptor antagonist β-funaltrexamine (β-FNA). In addition to the rotation of running wheels, horizontal locomotion, amounts of food intake and drinking, and access of food container were measured simultaneously by using a multi-configuration apparatus (0700/1900 light on/off). In naïve mice, horizontal locomotion increased day by day for three testing days. The increment was parallel to the increase in the rotation of running wheels but not to the number of accesses to food containers. The increase in the rotation of running wheels was sensitized, and the amount of food intake was unchanged in naïve mice. In mice group which was administered with a single injection of 5 mg/kg β-FNA, the locomotion and thus the rotation of the running wheels decreased especially in the first testing day. In contrast, no significant behavioral change was observed in mice under a continuous s.c. administration with osmotic mini-pumps (3.5 mg /kg of β-FNA for three days (71.5 h)). These results indicate that a transient increase in the levels of β-FNA reduced motivative behaviors in mice.