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Abstract Behavioral addictions can come in many forms, including overeating, gambling and overexercising. All addictions share a common mechanism involving activation of the natural reward circuit and reinforcement learning, but the extent to which motivation for natural and drug rewards share similar neurogenetic mechanisms remains unknown. A unique mouse genetic model in which four replicate lines of female mice were selectively bred (>76 generations) for high voluntary wheel running (High Runner or HR lines) alongside four non‐selected control (C) lines were used to test the hypothesis that high motivation for exercise is associated with greater reward for cocaine (20 mg/kg) and methylphenidate (10 mg/kg) using the conditioned place preference (CPP) test. HR mice run ~three times as many revolutions/day as C mice, but the extent to which they have increased motivation for other rewards is unknown. Both HR and C mice displayed significant CPP for cocaine and methylphenidate, but with no statistical difference between linetypes for either drug. Taken together, results suggest that selective breeding for increased voluntary running has modified the reward circuit in the brain in a way that increases motivation for running without affecting cocaine or methylphenidate reward.