Vagal nerve stimulation dynamically alters anxiety-like behavior in rats

Background: Electrical vagal nerve stimulation (VNS), at currents designed to target sensory, interoceptive neurons, decreases anxiety-like behavior. Objective/Hypothesis: We hypothesized that different VNS current intensities would differentially alter anxiety-like behavior through the activation o...

Full description

Saved in:
Bibliographic Details
Main Authors: A.G. Butler, J.K. Bassi, A.A. Connelly, M.R. Melo, A.M. Allen, S.J. McDougall
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Brain Stimulation
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1935861X25000208
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1823861216258293760
author A.G. Butler
J.K. Bassi
A.A. Connelly
M.R. Melo
A.M. Allen
S.J. McDougall
author_facet A.G. Butler
J.K. Bassi
A.A. Connelly
M.R. Melo
A.M. Allen
S.J. McDougall
author_sort A.G. Butler
collection DOAJ
description Background: Electrical vagal nerve stimulation (VNS), at currents designed to target sensory, interoceptive neurons, decreases anxiety-like behavior. Objective/Hypothesis: We hypothesized that different VNS current intensities would differentially alter anxiety-like behavior through the activation of distinct brainstem circuits. Methods: Electrodes were implanted to stimulate the left vagus nerve and to record diaphragm muscle and electrocardiogram activity. The VNS current required to elicit the A-fiber-mediated Hering-Breuer Reflex (HBR) was determined for each animal. Based on this threshold, animals received either sham stimulation or VNS at 1.5 (mid-intensity VNS) or 3 (higher-intensity VNS) times the threshold for HBR activation. Anxiety-like behavior was assessed using the elevated plus maze, open field test, and novelty-suppressed feeding test. Additionally, a place preference assay determined whether VNS is rewarding or aversive. Finally, a c-Fos assay was performed to evaluate VNS-driven neuronal activation within the brainstem. Results: Mid-intensity VNS reduced anxiety-like behavior in the elevated plus maze and open field test. Higher-intensity VNS was aversive during the place preference assay, confounding anxiety measures. Both intensities increased overall c-Fos expression in neurons within the nucleus of the solitary tract, but mid-intensity VNS specifically increased c-Fos expression in noradrenergic neurons within the nucleus of the solitary tract while decreasing it in the locus coeruleus. In contrast, higher-intensity VNS had no effect on c-Fos expression in noradrenergic neurons of either the nucleus of the solitary tract or locus coeruleus. Conclusion: Delivery of VNS induced reproducible, current intensity-dependent, effects on anxiety-like and aversive behavior in rats.
format Article
id doaj-art-d51d0e4108d54857acbadefc78ce5187
institution Kabale University
issn 1935-861X
language English
publishDate 2025-03-01
publisher Elsevier
record_format Article
series Brain Stimulation
spelling doaj-art-d51d0e4108d54857acbadefc78ce51872025-02-10T04:34:18ZengElsevierBrain Stimulation1935-861X2025-03-01182158170Vagal nerve stimulation dynamically alters anxiety-like behavior in ratsA.G. Butler0J.K. Bassi1A.A. Connelly2M.R. Melo3A.M. Allen4S.J. McDougall5Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, AustraliaDepartment of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, AustraliaDepartment of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, AustraliaDepartment of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, AustraliaFlorey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, Australia; Corresponding author. Department of Anatomy and Physiology University of Melbourne, Parkville, VIC, 3010, AustraliaFlorey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Corresponding author. Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3010, Australia.Background: Electrical vagal nerve stimulation (VNS), at currents designed to target sensory, interoceptive neurons, decreases anxiety-like behavior. Objective/Hypothesis: We hypothesized that different VNS current intensities would differentially alter anxiety-like behavior through the activation of distinct brainstem circuits. Methods: Electrodes were implanted to stimulate the left vagus nerve and to record diaphragm muscle and electrocardiogram activity. The VNS current required to elicit the A-fiber-mediated Hering-Breuer Reflex (HBR) was determined for each animal. Based on this threshold, animals received either sham stimulation or VNS at 1.5 (mid-intensity VNS) or 3 (higher-intensity VNS) times the threshold for HBR activation. Anxiety-like behavior was assessed using the elevated plus maze, open field test, and novelty-suppressed feeding test. Additionally, a place preference assay determined whether VNS is rewarding or aversive. Finally, a c-Fos assay was performed to evaluate VNS-driven neuronal activation within the brainstem. Results: Mid-intensity VNS reduced anxiety-like behavior in the elevated plus maze and open field test. Higher-intensity VNS was aversive during the place preference assay, confounding anxiety measures. Both intensities increased overall c-Fos expression in neurons within the nucleus of the solitary tract, but mid-intensity VNS specifically increased c-Fos expression in noradrenergic neurons within the nucleus of the solitary tract while decreasing it in the locus coeruleus. In contrast, higher-intensity VNS had no effect on c-Fos expression in noradrenergic neurons of either the nucleus of the solitary tract or locus coeruleus. Conclusion: Delivery of VNS induced reproducible, current intensity-dependent, effects on anxiety-like and aversive behavior in rats.http://www.sciencedirect.com/science/article/pii/S1935861X25000208NeuromodulationAfferentAutonomicAnxiolyticAnxiogenicState dependent
spellingShingle A.G. Butler
J.K. Bassi
A.A. Connelly
M.R. Melo
A.M. Allen
S.J. McDougall
Vagal nerve stimulation dynamically alters anxiety-like behavior in rats
Brain Stimulation
Neuromodulation
Afferent
Autonomic
Anxiolytic
Anxiogenic
State dependent
title Vagal nerve stimulation dynamically alters anxiety-like behavior in rats
title_full Vagal nerve stimulation dynamically alters anxiety-like behavior in rats
title_fullStr Vagal nerve stimulation dynamically alters anxiety-like behavior in rats
title_full_unstemmed Vagal nerve stimulation dynamically alters anxiety-like behavior in rats
title_short Vagal nerve stimulation dynamically alters anxiety-like behavior in rats
title_sort vagal nerve stimulation dynamically alters anxiety like behavior in rats
topic Neuromodulation
Afferent
Autonomic
Anxiolytic
Anxiogenic
State dependent
url http://www.sciencedirect.com/science/article/pii/S1935861X25000208
work_keys_str_mv AT agbutler vagalnervestimulationdynamicallyaltersanxietylikebehaviorinrats
AT jkbassi vagalnervestimulationdynamicallyaltersanxietylikebehaviorinrats
AT aaconnelly vagalnervestimulationdynamicallyaltersanxietylikebehaviorinrats
AT mrmelo vagalnervestimulationdynamicallyaltersanxietylikebehaviorinrats
AT amallen vagalnervestimulationdynamicallyaltersanxietylikebehaviorinrats
AT sjmcdougall vagalnervestimulationdynamicallyaltersanxietylikebehaviorinrats