Excessive training alters hippocampal tyrosine hydroxylase and dopamine homeostasis in mice.

Excessive training, defined by repeated high-intensity exercise with insufficient recovery, leads to persistent fatigue, performance decline, and mood alterations. Monoaminergic signaling, particularly serotonin and dopamine, is crucial for regulating effort perception and exercise tolerance. The hippocampus, a brain region highly responsive to exercise, integrates serotonergic and dopaminergic inputs, playing a central role in mood and cognition. However, how acute and chronic excessive training affects hippocampal monoaminergic dynamics remains unclear. We investigated the effects of acute and chronic exhaustive exercise on hippocampal serotonin, dopamine, tyrosine hydroxylase (TyrH), and vesicular monoamine transporter 2 (VMAT2). C57BL/6 male mice underwent either a single exhaustive bout (acute protocol) or an 8-week progressively intensified treadmill regimen leading to excessive workload (chronic protocol). Hippocampal samples were collected at four time points after acute exercise and during active and rest phases after chronic training. In the acute protocol, dopamine levels increased immediately post-exercise, with reduced TyrH expression, while serotonin and VMAT2 remained unchanged. In contrast, chronic training sustained hippocampal dopamine elevation and increased TyrH expression, resulting in a reduced serotonin/dopamine ratio during rest. These findings indicate that prolonged exhaustive training is associated with dopamine-related changes in the hippocampus, accompanied by higher TyrH protein levels during the resting phase in mice.