The 5-HT3 receptor is essential for exercise-induced hippocampal neurogenesis and antidepressant effects

• Published in: Molecular psychiatry Vol. 20; no. 11; pp. 1428 - 1437
• Main Authors: Kondo, M, Nakamura, Y, Ishida, Y, Shimada, S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-11-2015; Nature Publishing Group
• Subjects: 631/378; 631/477; Animals; Antidepressants; Antidepressive Agents - pharmacology; Behavior; Behavioral Sciences; Biological Psychology; Brain; Bromodeoxyuridine - metabolism; Cell growth; Cell Proliferation - drug effects; Cell Proliferation - physiology; Conditioning (Psychology) - drug effects; Conditioning (Psychology) - physiology; Experiments; Exploratory Behavior - drug effects; Fear - drug effects; Fear - psychology; Functional anatomy; Growth factors; Hindlimb Suspension; Hippocampus; Hippocampus - cytology; Hippocampus - drug effects; Learning behavior; Medicine; Medicine & Public Health; Memory; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microtubule-Associated Proteins - metabolism; Mood; Morphology; Neurogenesis; Neurogenesis - drug effects; Neurogenesis - physiology; Neuropeptides - metabolism; Neurosciences; original-article; Pharmacotherapy; Phosphopyruvate Hydratase - metabolism; Physical Conditioning, Animal - physiology; Piperidines - pharmacology; Psychiatry; Receptors, Serotonin, 5-HT3 - genetics; Receptors, Serotonin, 5-HT3 - metabolism; Serotonin; Serotonin Agents - pharmacology; Serotonin S3 receptors; Structure-function relationships; Swimming - psychology; United States > US; Japan
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2014.153

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.