Clarification of how exercise helps prevent and treat depression

Exercise increases serotonin levels in the brain

Nov 18, 2014

A group of researchers led by KONDO Makoto , Assistant Professor, and SHIMADA Shoichi , Professor, at the Department of Neuroscience and Cell Biology, Department of Anatomy, Graduate School of Medicine, Osaka University, have clarified that type 3 serotonin receptors play a pivotal role in antidepressant effects and hippocampal neurongenesis induced by exercise.

Exercise induces various changes in neurons and molecules in the animal brain and has beneficial effects on animal behavior. For example, in mice and rats, it is known that exercise induces beneficial effects such as hippocampal neurongenesis, a decrease in depression, and improvement of learning behavior. Likewise, in humans, exercise is a means for the prevention and treatment of disorders associated with adult lifestyles, depression, and dementia; however, exactly how such beneficial effects take place in the brain has been unknown.

Serotonin is one of the substances associated with neural transmission in the brain and is responsible for mood and memory. It is also thought to play a role in mental conditions such as depression. It has been known that exercise increases serotonin levels in the brain; however, how serotonin works has been unknown.

This group paid attention to serotonin receptors, 5-HT type 3A receptors, and decided to clarify the role of such by using mice in research on how exercise induces changes to the brain. Using serotonin receptor-deficient mice, this group examined neurons in the hippocampus and depressive-like behavior after exercise, clarifying that type 3 serotonin receptors play a pivotal role in antidepressant effects and hippocampal neurongenesis induced by exercise.

This group's findings will make a contribution to the prevention of mental disorders such as depression as well as the maintenance and promotion of mental health. Furthermore, as exercise is useful in the treatment of depression, their findings will contribute to a lessening of the distress of persons suffering from depression.


Exercise has a variety of beneficial effects on brain structure and function, such as hippocampal neurogenesis, mood and memory. Previous studies have shown that exercise enhances hippocampal neurogenesis, induces antidepressant effects and improves learning behavior. Brain serotonin (5-hydroxytryptamine, 5-HT) levels increase following exercise, and the 5-HT system has been suggested to have an important role in these exercise-induced neuronal effects. However, the precise mechanism remains unclear. In this study, analysis of the 5-HT type 3A receptor subunit-deficient (htr3a − / − ) mice revealed that lack of the 5-HT type 3 (5-HT 3 ) receptor resulted in loss of exercise-induced hippocampal neurogenesis and antidepressant effects, but not of learning enhancement. Furthermore, stimulation of the 5-HT 3 receptor promoted neurogenesis. These findings demonstrate that the 5-HT 3 receptor is the critical target of 5-HT action in the brain following exercise, and is indispensable for hippocampal neurogenesis and antidepressant effects induced by exercise. This is the first report of a pivotal 5-HT receptor subtype that has a fundamental role in exercise-induced morphological changes and psychological effects.

To learn more about this research, please view the full research report entitled " The 5-HT3 receptor is essential for exercise-induced hippocampal neurogenesis and antidepressant effects " at this page of the Molecular Psychiatry website.

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