A single, half-hour session of moderate exercise is enough to confer an immediate mood-boosting effect, and now scientists have figured out why.

In mice – and likely humans – that boost comes from the release of a hormone called adiponectin, which travels into the brain and sparks activity in a region associated with emotional regulation. The result is a lift in mood that could hang around for hours, although the duration has yet to be measured in humans.

There are some pretty incredible implications here. For people who can exercise, even one workout could offer immediate relief for symptoms of anxiety or depression.

The same mechanism could inspire a class of new, fast-acting antidepressant drugs that take effect much more quickly than traditional treatments such as SSRIs.

"Rapid-acting antidepressant treatments that offer sustained effects and minimal side effects remain scarce," neurobiologist Sonata Suk-yu Yau of Hong Kong Polytechnic University told Psypost.

"This study provides clinical evidence for the effectiveness of a single session of exercise in alleviating depressive symptoms."

Ongoing physical activity is widely recognized as a means of both treating and preventing mild to moderate depression. However, not much is known about the effects of a single bout of moderate exercise – a nice jog, for example.

Emerging evidence seems to suggest that bursts of exercise have a positive effect on individuals with depression; Yau and her colleagues wanted to quantify that effect and identify the reason behind it.

They recruited 40 adult humans between the ages of 18 and 40, and a few dozen mice across multiple experimental groups, and got them to work exercising.

The humans were the easy part. Each participant filled out a Profile of Mood States survey to assess their mood. Then, they ran on a treadmill for 30 minutes while wearing a heart rate monitor. After exercising, they immediately retook the survey.

Participants both with and without symptoms of anxiety and depression demonstrated a significant mood lift, with symptomatic participants reporting lower anger, confusion, fatigue, depression, and anxiety overall. Meanwhile, esteem and vigor rose across all participants.

To figure out why, the researchers turned to the mice. This is where it becomes unpleasant. To induce depression-like symptoms, some of the animals were put through several weeks of a protocol called chronic unpredictable stress.

This means the mice are subjected to prolonged exposure to a variety of inconsistent and unpredictable stressors, such as wet bedding, restraint, a tilted cage, or holding a mouse's foot to an electrified pad for five minutes.

It results in reductions in grooming behavior, exploration, and curiosity, and an increase in immobility when put through physical tests, similar to symptoms of depression in humans.

Some mice were not subjected to this protocol to serve as the control group.

Then, the mice were given a similar burst of moderate exercise on a treadmill, and their behavior was assessed. It worked: both stressed and unstressed mice showed behaviors associated with an elevated mood, including grooming and increased mobility, and spent a longer time attempting to swim when placed in water.

These effects were measured at 2 hours post-exercise, and persisted for at least 24 hours; by 48 hours, the effects had subsided.

To figure out why, the researchers euthanized freshly exercised mice and studied them. They found higher levels of a hormone called adiponectin in both the blood and the medial prefrontal cortex of the mice after exercise, a region of the brain that includes the anterior cingulate cortex, a crucial region for emotion regulation.

Brain imaging and mapping revealed that adiponectin switches on a receptor in certain neurons called AdipoR1; knocking out that receptor in those neurons in another mouse cohort eradicated the behaviors associated with a positive mood boost.

On further investigation, the researchers found AdipoR1 activates a protein called APPL1 that moves into the neuron's nucleus, triggering a cascade of molecular changes that help build or strengthen synapses.

These neurons also formed new dendritic spines – an effect that disappeared when APPL1 was blocked – suggesting that they, too, play a role in the mood-boosting effects of exercise. A similar dendritic disinhibition is triggered by ketamine, which could hold some clues about how it works.

The key here, however, seems to be the activation of AdipoR1 – it's like the switch that turns on that post-exercise bliss-out.

That suggests a strong target for therapeutic intervention; indeed, scientists have been investigating the potential of synthetic adiponectin receptor agonist AdipoRon as a treatment for depression, although it has not yet been tested in humans.

Nevertheless, the study does show a clear mechanism for the mood boost conferred by a workout, suggesting that exercise may be a valid treatment regimen for individuals who struggle with finding an appropriate medication.

"Ultimately, our objective is to develop population-based guidelines with optimal single-bout exercise prescriptions for mood improvement, serving as an effective strategy to prevent the development of depression," Yau said.