Chronic voluntary exercise induces plasticity of noradrenaline-activated dopamine D1-like receptor signaling

Abstract Physical exercise has lasting positive influence on mental health. However, its cellular substrate remains to be elucidated. Recently, dopamine D1-like receptor activation induced by noradrenaline has been suggested to underlie exercise-dependent augmentation of antidepressant effects. The...

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Bibliographic Details
Main Author: Katsunori Kobayashi
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Molecular Brain
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Online Access:https://doi.org/10.1186/s13041-025-01219-5
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Summary:Abstract Physical exercise has lasting positive influence on mental health. However, its cellular substrate remains to be elucidated. Recently, dopamine D1-like receptor activation induced by noradrenaline has been suggested to underlie exercise-dependent augmentation of antidepressant effects. The present study demonstrates that exercise induces a long-term enhancement of this atypical catecholaminergic signaling. Noradrenaline potentiates hippocampal mossy fiber synaptic transmission by activating D1-like receptors in mice. Voluntary exercise by wheel running enhanced this noradrenaline-D1-like receptor signaling within 5 days. The enhancement of the noradrenaline-D1-like receptor signaling did not require the integrity of noradrenergic fibers and was maintained for more than 2 weeks after cessation of wheel running. Notably, the effect of exercise was more robustly seen in D1-like receptor signaling activated by noradrenaline as compared with dopamine, indicating particular responsiveness of the noradrenaline-activated D1-like receptor signaling to exercise. These results suggest that exercise could exert lasting influence on brain functioning via plasticity of the hippocampal noradrenaline-D1-like receptor signaling.
ISSN:1756-6606