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

## TL;DR

Chronic exercise in mice enhances noradrenaline-activated dopamine receptor signaling in the brain, which may explain its long-term mental health benefits.

## Contribution

The study reveals that voluntary exercise induces lasting plasticity in noradrenaline-activated D1-like receptor signaling in the hippocampus.

## Key findings

- Voluntary exercise enhances noradrenaline-D1-like receptor signaling within 5 days.
- The enhancement persists for over 2 weeks after exercise cessation.
- Noradrenaline-activated D1-like receptor signaling is more responsive to exercise than dopamine-activated 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 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.

The online version contains supplementary material available at 10.1186/s13041-025-01219-5.