An appetite for running may be fuelled by a primitive urge to seek out food, research suggests.
The link between hunger and desire for exercise may also contribute to the "high" experienced by dedicated joggers, say scientists.
A study of mice running on treadmills highlighted the role played by leptin, a satiety hormone responsible for the feeling of being "full".
The findings suggest that falling leptin levels send a "hunger" signal to pleasure circuits in the brain that generate the rewarding effects of running.
In this way, the hormone regulates the desire to eat and physical activity.
Lead scientist Professor Stephanie Fulton, from the University of Montreal in Canada, said: "We think that a fall in leptin levels increases motivation for physical activity as a means to enhance exploration and the pursuit of food.
"Our study also suggests that people with lower fat-adjusted leptin levels, such as high-performance marathon runners, could potentially be more susceptible to the rewarding effects of running and thus possibly more inclined to exercise."
Leptin, derived from fat cells, tells the brain when the body has enough fuel and energy.
But its effects are more complicated than that, involving the brain mechanism for rewarding beneficial behaviour - such as eating - that is largely driven by the nerve-signalling chemical dopamine.
Prof Fulton's team tested genetically engineered mice lacking a protein called STAT3 that relays the leptin signal to dopamine-releasing neurons.
Whereas normal mice ran six kilometres (3.7 miles) per day on the running wheel, the STAT3-deficient animals kept going for 11 kilometres (6.8 miles).
Lacking STAT3 also blunted the reward-seeking effects of dopamine in the modified mice.
Prof Fulton said: "Previous studies have clearly shown a correlation between leptin and marathon run times. The lower leptin levels are, the better the performance. Our study on mice suggests that this molecule is also involved in the rewarding effects experienced when we do physical exercise.
"We speculate that for humans, low leptin levels increase motivation to exercise and make it easier to get a runner's high."
The findings, published in the journal Cell Metabolism, could have implications for treating the "slimming disease" anorexia, said the scientists.
Previous research has shown that leptin signalling inhibits wheel running in a rat model of anorexia-induced hyperactivity.
People with anorexia are both restless and hyperactive, and lacking in leptin.
"We speculate that the mechanism described in this work could potentially underlie the hyperactivity associated with anorexia," said Prof Fulton.