Electrophysiological and neurochemical effects of long-term vagus nerve stimulation on the rat monoaminergic systems
Open accessAbstract
Vagus nerve stimulation (VNS) is an adjunctive treatment for resistant epilepsy and depression. Electrophysiological recordings in the rat brain have already shown that chronic VNS increases norepinephrine (NE) neuronal firing activity and, subsequently, that of serotonin (5-HT) neurons through an activation of their excitatory α1-adrenoceptors. Long-term VNS was shown to increase the tonic activation of post-synaptic 5-HT1A receptors in the hippocampus. This study was aimed at examining the effect of VNS on extracellular 5-HT, NE and dopamine (DA) levels in different brain areas using in vivo microdialysis, on NE transmission in the hippocampus, and DA neuronal firing activity using electrophysiology. Rats were implanted with a VNS device and stimulated for 14 d with standard parameters used in treatment-resistant depression (0.25 mA, 20 Hz, 500 µs, 30 s on–5 min off). The results of the present study revealed that 2-wk VNS significantly increased extracellular NE levels in the prefrontal cortex and the hippocampus and enhanced the tonic activation of post-synaptic α2-adrenoceptors on pyramidal neurons. The electrophysiological experiments revealed a significant decrease in ventral tegmental area DA neuronal firing rate after long-term VNS; extracellular DA levels were nevertheless increased in the prefrontal cortex and nucleus accumbens. Chronic VNS significantly increased extracellular 5-HT levels in the dorsal raphe but not in the hippocampus and prefrontal cortex. In conclusion, the effect of VNS in increasing the transmission of monoaminergic systems targeted in the treatment of resistant depression should be involved, at least in part, in its antidepressant properties observed in patients not responding to many antidepressant strategies.
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Chronic VNS is associated with increased extracellular levels of serotonin in the dorsal raphe.
“Thus, chronic VNS was associated with increased extracellular levels of serotonin in the dorsal raphe (90).”
From Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders (2018) · cites this paper as [90]
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- Authors
- Manta, S., El Mansari, M., Debonnel, G., & Blier, P.
- Affiliations
- Institute of Mental Health Research (CA)
- University of Ottawa Institute of Mental Health Research, Ottawa, Ontario, Canada
- McGill University (CA)
- University of Ottawa (CA)
- Corresponding author
- Blier, Pierre
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-04-17
- Volume
- 16
- Issue
- 2
- Pages
- 459-470
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2135537366
- Cited by
- 192
- References
- 68
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 16 · 2023: 21 · 2022: 20 · 2021: 22 · 2020: 16 · 2019: 7 · 2018: 11 · 2017: 10 · 2016: 6 · 2015: 10 · 2014: 9 · 2013: 7 · 2012: 2
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- University of Ottawa
- Servier
- H. Lundbeck A/S
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- vagus nerve stimulation, monoaminergic systems, norepinephrine, serotonin, dopamine, treatment-resistant depression, alpha2-adrenoceptors, alpha1-adrenoceptors, 5-HT1A receptor, ventral tegmental area, dorsal raphe nucleus, prefrontal cortex, hippocampus, nucleus accumbens, extracellular neurotransmitter levels, neuronal firing rate, antidepressant mechanism
- MeSH terms
- Action Potentials, Afferent Pathways, Analysis of Variance, Animals, Brain, Chromatography, High Pressure Liquid, Dose-Response Relationship, Drug, Male, Neurons, Time Factors, Biogenic Monoamines, Rats, Sprague-Dawley, Microdialysis, Extracellular Fluid, Rats, Vagus Nerve Stimulation
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