The joy of running. That sense of well-being, freedom and extra energy that runners often experience is not just a matter of endorphins. A study at the University of Montreal Hospital Research Centre (CRCHUM) shows that the "runner's high" phenomenon is also caused by dopamine, an important neurotransmitter for motivation.

"We discovered that the rewarding effects of endurance activity are modulated by leptin, a key hormone in metabolism. Leptin inhibits physical activity through dopamine neurons in the brain," said Stephanie Fulton, a researcher at the CRCHUM and lead author of an article published in the journal Cell Metabolism.

Secreted by adipose tissue, leptin helps control the feeling of satiety. This hormone also influences physical activity. "The more fat there is, the more leptin there is and and the less we feel like eating. Our findings now show that this hormone also plays a vital role in motivation to run, which may be related to searching for food," explained Stephanie Fulton, who is also a professor at Université de Montréal's Department of Nutrition.

Hormone signals that modulate feeding and exercise are in fact believed to be closely linked. Endurance running capacity in mammals, particularly humans, is thought to have evolved to maximize the chances of finding food. This study suggests that leptin plays a critical role both in regulating energy balance and encouraging behaviours that are "rewarding" for the person's metabolism, i.e., engaging in physical activity to find food.

The researchers studied voluntary wheel running in mice in cages. These mice can run up to seven kilometres a day. In a laboratory, the physical activity of normal mice was compared with that of mice who underwent a genetic modification to suppress a molecule activated by leptin, STAT3 (signal transducer and activator of transcription-3). The STAT3 molecule is found in the neurons that synthesize dopamine in the midbrain. This "mesolimbic dopaminergic pathway" is a like a motivational highway in the brain.

"Mice that do not have the STAT3 molecule in the dopaminergic neurons run substantially more. Conversely, normal mice are less active because leptin then activates STAT3 in the dopamine neurons, signalling that energy reserves in the body are sufficient and that there is no need to get active and go looking for food," explained Maria Fernanda Fernandes, first author of the study.

And is leptin as important for motivation to be active in humans? Yes. "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," summed up Stephanie Fulton.

Mice, humans and mammals in general are thought to have evolved to increase the return on effective food acquisition behaviours. Ultimately, hormones are sending the brain a clear message: when food is scarce, it's fun to run to chase some down.