Scientists have discovered unexpected changes in brain chemistry following intense, prolonged exercise in mice.
Two days after a stress test, mice subjected to weeks of grueling training still had elevated dopamine levels in the hippocampus, a brain region involved in memory and emotional regulation. The results suggest that excessive exercise without adequate recovery can produce lasting changes in brain chemistry.
The study, published in the journal Neurosciencewas carried out by researchers in Brazil. Because dopamine helps regulate motivation and alertness, the findings raise the question of whether similar disruptions might contribute to sleep problems, anxiety, and persistent fatigue in overtrained athletes. However, these possible effects have not been demonstrated in humans.
What happens to the brain after excessive exercise?
To study how different levels of physical exertion affect the brain, researchers compared mice subjected to two exercise protocols. One group completed a single session on the treadmill until exhaustion. The other followed eight weeks of increasingly demanding training designed to simulate the physical exertion associated with overtraining syndrome.
During the final week, the heavily trained mice exercised twice a day, with only four hours between sessions. The researchers then examined the animals’ hippocampi, measuring dopamine, serotonin, and proteins involved in the production and regulation of neurotransmitters.
Mice that completed a single strenuous run showed an increase in dopamine shortly afterward. In contrast, chronically trained animals had elevated dopamine levels even 48 hours after their performance test, during a period intended for recovery. Levels of tyrosine hydroxylase (TyrH), an enzyme essential for the synthesis of dopamine, also remained elevated.
Dopamine changes without a similar increase in serotonin
Dopamine is involved in several functions, including motivation, reward processing, and arousal. Its presence is not harmful in itself, but changes in its regulation could affect brain activity during periods when the body would normally be recovering.
Interestingly, the researchers found no significant changes in serotonin levels. Serotonin has long been studied as a possible contributor to exercise-related fatigue, but these findings suggest that the neurochemical effects of excessive training cannot be explained by serotonin alone.
“Our results show that excessive exercise not only affects skeletal muscles but also has a pronounced impact on the brain,” said Alisson Luiz da Rocha, first author of the study. He carried out this research during his doctoral studies at the Ribeirão Preto School of Physical Education and Sports of the University of São Paulo (EEFERP-USP), with the support of FAPESP.
Could these brain changes help explain the symptoms of overtraining?
Overtraining syndrome occurs when prolonged physical demands exceed the body’s ability to recover, which can lead to decreased athletic performance, chronic fatigue, muscle pain, loss of appetite, increased injuries, and changes in immune and metabolic function. Researchers suspect that changes in brain signaling may also contribute to certain symptoms.
Adelino Sanchez Ramos da Silva, a professor at EEFERP-USP who coordinated the study, suggested that similar dopamine disorders in humans could help explain links between excessive training and sleep disorders. However, the researchers did not directly measure sleep, anxiety, or alertness in the mice. The results therefore cannot establish a link between the chemical changes observed and these symptoms.
The research team is currently participating in an international project aimed at identifying which biological systems begin to show abnormal responses when excessive exercise interferes with the body’s usual adaptations to training. Such work could help clarify how beneficial physical activity progresses to a state of insufficient recovery and impaired performance.
Reference: “Excessive training alters hippocampal tyrosine hydroxylase and dopamine homeostasis in mice” by Alisson Luiz da Rocha, João Pedro Floriano, Ana Paula Pinto, Dennys Esper Cintra, Eduardo Rochete Ropelle, Ellen Cristini de Freitas, José Rodrigo Pauli and Adelino Sanchez Ramos da Silva, August 4, 2026, Neuroscience.
DOI: 10.1016/j.neuroscience.2026.08.006
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