One 30‑Minute Workout Can Lift Mood Immediately — Scientists Identify the Hormone and Brain Circuit

A single 30‑minute session of moderate exercise can produce an immediate, measurable improvement in mood. New research links this rapid benefit to the hormone adiponectin, which enters the brain after exercise and activates a specific receptor and molecular cascade in the medial prefrontal cortex — a region involved in emotional regulation. In mice the effect lasted at least 24 hours, and a small human experiment showed immediate mood improvements after one workout.

Human study: immediate mood changes

The human portion of the study enrolled 40 adults aged 18–40. Participants completed a standard Profile of Mood States questionnaire, ran on a treadmill for 30 minutes while wearing heart‑rate monitors, and then immediately repeated the questionnaire. Both people with and without symptoms of anxiety or depression reported significant, immediate improvements: reductions in anger, confusion, fatigue, depression and anxiety for symptomatic participants, and increases in vigor and self‑esteem across the group.

Mouse experiments and biological mechanism

To probe the underlying biology, researchers used a mouse model. Some animals were exposed to several weeks of chronic unpredictable stress (a standard research protocol that includes varied stressors such as wet bedding, restraint, cage disturbance and brief mild foot shocks) to induce depression‑like behaviours; other mice served as unstressed controls. After a single session of moderate treadmill exercise, both stressed and unstressed mice displayed behaviours consistent with an elevated mood — more grooming, greater mobility, and longer attempts to swim.

These behavioural effects were detected two hours after exercise, persisted for at least 24 hours, and had largely subsided by 48 hours.

Adiponectin → AdipoR1 → APPL1: the molecular cascade

Biochemical and anatomical analyses found that exercise increased adiponectin levels in the blood and in the medial prefrontal cortex. Adiponectin engages a neuronal receptor called AdipoR1; when AdipoR1 was genetically removed from those neurons, the exercise‑related behavioural improvements disappeared. Further work showed that AdipoR1 activation mobilises the protein APPL1 to the neuronal nucleus, triggering molecular changes that strengthen synaptic connections and promote formation of new dendritic spines. Blocking APPL1 prevented these structural changes. The authors note that some features of this synaptic reconfiguration resemble effects seen with rapid‑acting treatments such as ketamine, suggesting possible mechanistic overlap.

Implications

The findings explain how a single workout can produce a rapid mood lift and identify a clear biological target — AdipoR1 signalling — for potential therapeutic intervention. Researchers are exploring synthetic adiponectin receptor agonists, such as AdipoRon, as candidate fast‑acting antidepressants, though such compounds have not yet been tested in humans for this purpose. The study also supports the idea that a single, prescribed bout of exercise might be used as a low‑risk, immediately available strategy to relieve anxiety or depressive symptoms while longer‑term treatments are implemented.

Quote: Sonata Suk‑yu Yau of Hong Kong Polytechnic University said, "Rapid‑acting antidepressant treatments that offer sustained effects and minimal side effects remain scarce. This study provides clinical evidence for the effectiveness of a single session of exercise in alleviating depressive symptoms."

The research was published in the journal Molecular Psychiatry.