Lateral Habenula Regulates Cardiovascular Autonomic Responses via the Serotonergic System in Rats.

Tri Huu Doan,Tadachika Koganezawa,Yuma Sato,Masayuki Matsumoto

doi:10.3389/fnins.2021.655617

Abstract

The lateral habenula (LHb) plays essential roles in behavioral responses to stressful events. Stress is tightly linked to autonomic responses such as cardiovascular responses, yet how the LHb regulates these responses is not well understood. To address this issue, we electrically stimulated the LHb in rats, measured its effects on heart rate (HR) and mean arterial pressure (MAP), and investigated the neural circuits that mediate these LHb-induced cardiovascular responses via the autonomic nervous system. We observed that stimulation of the LHb induced bradycardia and pressor responses, whereas stimulation of the adjacent areas changed neither the HR nor the MAP. Bilateral vagotomy and administration of a muscarinic receptor antagonist suppressed the LHb stimulation effect on the HR but not on the MAP, whereas administration of a β-adrenoceptor antagonist partly attenuated the effect on the MAP but not on the HR. Thus, the LHb-induced cardiovascular responses of the HR and the MAP were likely caused by activations of the cardiac parasympathetic nerves and the cardiovascular sympathetic nerves, respectively. Furthermore, administration of a non-selective 5-HT receptor antagonist significantly attenuated the LHb stimulation effects on both the MAP and the HR. A 5-HT2 receptor antagonist also attenuated the LHb stimulation effects. A low dose of a 5-HT1A receptor antagonist enhanced the LHb stimulation effects, but a high dose of the drug attenuated them. 5-HT1B and 5-HT1D receptor antagonists as well as a 5-HT7 receptor antagonist did not affect the LHb stimulation effects. Taken together, our findings suggest that the LHb regulates autonomic cardiovascular responses at least partly through the serotonergic system, particularly via the 5-HT1A and 5-HT2 receptors.

Highlights

The autonomic nervous system, especially the autonomic cardiovascular system, plays critical roles to ensure the survival of animals, including humans, when they face perceived threats in the environment
To investigate whether the lateral habenula (LHb) is involved in cardiovascular regulation, we examined the effects of electrical stimulation of the LHb on heart rate (HR) and mean arterial pressure (MAP)
All the outside stimulation sites that induced the change in HR or MAP were adjacent to the border of the LHb

Summary

Introduction

The autonomic nervous system, especially the autonomic cardiovascular system, plays critical roles to ensure the survival of animals, including humans, when they face perceived threats in the environment. The parasympathetic nervous system causes opposite effects, which include reduction of HR and contractility, and decreases cardiac output and blood pressure These systems are mainly regulated by two mechanisms: (1) a reflex originating from peripheral sensory neuron impulses and (2) a central mechanism, or “central command,” which adapts the blood circulation via modulation from higher centers in the brain (Dampney, 2016). An essential factor that elicits the central command is acute psychological stimuli, such as smell and sight of predators, which indicate threatening and stressful occasions and need to be responded to as fast as possible The brain analyzes these acute psychological stimuli and chooses appropriate behavioral responses to them depending on the environmental demands. Passive coping strategies, which include immobilization or freezing, are activated when the stimuli are inescapable, and these strategies are commonly accompanied by activation of the sympathetic and parasympathetic nervous systems along with causing bradycardia and elevation of systemic blood pressure (Schenberg et al, 1993; Schadt and Hasser, 1998; Carrive, 2006)

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