The brainstem noradrenergic systems in stress, anxiety and depression
Abstract
The locus coeruleus (LC) is regarded as a part of the central 'stress circuitry' because robust activation of the LC has been reported after stressful stimuli in experimental animals. A considerable amount of clinical evidence also suggests the relationship between the central noradrenergic (NAergic) system and fear/anxiety states or depression. However, previous animal studies have not been able to demonstrate unequivocally the involvement of the NAergic system in mediating fear or anxiety. The forebrain structures, including the hypothalamus, receive massive inputs from the medullary NAergic nuclei via the ventral NAergic bundle (VNAB). The VNAB has been implicated in the neuroendocrine stress axis mainly through its action on the corticotrophin-releasing factor neurones in the paraventricular nucleus of the hypothalamus. Novel tools were introduced that are capable of disrupting the NAergic system more selectively and/or thoroughly than the neurotoxins employed in previous studies: the anti-dopamine-beta hydroxylase (DBH)-saporin is an immunotoxin that is taken up from nerve endings and disrupt the NAergic neurones in a retrograde manner. The genetically DBH-depleted mice were also introduced, which lack endogenous noradrenaline. Owing to the rapid development of functional imaging technique, visualisation of the emotional phenomena has become possible in human subjects. Along with the advent of these technologies, endeavors have been continued to unravel the functional re…
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Most forebrain monoamines originate in the midbrain: serotonin in the dorsal raphe, norepinephrine in the locus coeruleus, and dopamine in the VTA or substantia nigra pars compacta.
“The endogenous source for the majority of monoamines in the forebrain come from the midbrain, with serotonin, norepinephrine, and dopamine arising from the dorsal raphe (DR), locus coeruleus (LC), and ventral tegmental area (VTA) or substantia nigra pars compacta, respectively”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Itoi & Sugimoto, 2010
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- Authors
- Itoi, K., & Sugimoto, N.
- Affiliations
- Tohoku University (JP)
- Corresponding author
- Itoi, K.
- ORCID
- Itoi, K.
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2010-04-19
- Volume
- 22
- Issue
- 5
- Pages
- 355-361
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- OpenAlex
- W2006593760
- Cited by
- 207
- References
- 2
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 12 · 2023: 8 · 2022: 15 · 2021: 12 · 2020: 16 · 2019: 4 · 2018: 7 · 2017: 11 · 2016: 14 · 2015: 18 · 2014: 19 · 2013: 17 · 2012: 16
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- locus coeruleus, noradrenergic system, brainstem, stress, anxiety, depression, ventral noradrenergic bundle, hypothalamus, paraventricular nucleus, corticotropin-releasing factor, dopamine beta-hydroxylase, saporin, norepinephrine depletion, fear
- MeSH terms
- Animals, Anxiety, Brain Stem, Depression, Norepinephrine, Stress, Psychological, Mice
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