# The lateral habenula regulates stress-related respiratory responses via the monoaminergic system

## TL;DR

The lateral habenula influences breathing during stress through dopamine and serotonin systems in the brain.

## Contribution

This study reveals a novel neural pathway linking the lateral habenula to stress-induced respiratory changes via monoaminergic systems.

## Key findings

- LHb stimulation increases respiratory frequency and minute ventilation in anesthetized rats.
- Dopaminergic modulation from the VTA is crucial for LHb-induced respiratory responses.
- Serotonergic antagonism accelerates LHb-induced respiratory frequency while reducing thoracic movement.

## Abstract

Psychologic stress induces behavioral and autonomic responses such as acceleration of respiration. The lateral habenula (LHb) is noted to be involved in stress-induced behavioral responses. However, its involvement in stress-induced respiratory responses is unknown. In this study, we aimed to analyze whether and how the LHb regulates respiration. Electrical stimulation of the LHb of anesthetized Wistar male rats increased respiratory frequency and minute ventilation, calculated by respiratory frequency × thoracic movement amplitude. Systemic administration of a dopaminergic receptor antagonist, clozapine, suppressed the LHb-induced respiratory responses. On the other hand, administration of a serotonergic receptor antagonist, methysergide, significantly accelerated the LHb-induced increase in respiratory frequency, together with suppressing the thoracic movement amplitude. To clarify the source of dopaminergic modulation, we inhibited the ventral tegmental area (VTA), which contains dopaminergic neurons and receives inputs from the LHb, by administering microinjections of a GABAA agonist, muscimol. The bilateral inhibition of the VTA almost abolished the LHb-induced respiratory responses. These results suggest that LHb activation causes respiration acceleration, mainly mediated by dopaminergic neurons in the VTA and suppressively modulated by the serotonergic system. Neural circuits originating in the LHb may be a key modulator for respiration during psychological stress.

The online version contains supplementary material available at 10.1007/s00424-024-03043-7.