The effect of exposure of male mice to a horizontal running wheel (Fast-Trac™) on conditioned place preference (CPP) and hyperlocomotion induced by methamphetamine (METH) was determined. In the first experiment eleven-week-old male ICR mice were divided into three groups and exposed to three different environments (housed individually with (group A) or without a running wheel (group B), or housed in a group of eight mice without a running wheel (group C)) for two weeks except during periods of CPP conditioning and testing procedures. Administration of METH (0.5 mg/kg, i.p.) every other day during three conditioning sessions, with saline conditioning sessions in the other compartment on alternate days (ie, saline/METH conditioning), induced a significant CPP, compared to saline/saline conditioning, in mice of groups A and C, but not B. The increased CPP for METH was significantly attenuated by additional 5-day (drug-free)-exposure to a running wheel in mice of group A (but not group C). In the second experiment, pre-exposure of another set of mice to a running wheel for three days did not affect a subsequent METH (1.0 mg/kg)- or saline-induced horizontal locomotion or rearing, compared with the locomotor activities observed in mice without an experience of a running wheel. These observations suggest that experience of a running wheel may selectively facilitate an attenuation of drug-seeking behavior.