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The Modulatory Role of the Lateral Septum on Neuroendocrine and Behavioral Stress Responses
Open accessAbstract
The lateral septum (LS) has been shown to have a key role in emotional processes and stress responses. However, the exact role of the LS on stress modulation is not clear, as previous lesion studies mostly used electrolytic lesions, thereby destroying the whole septal area, including medial components and/or fibers of passage. The aim of the present study was therefore, to investigate the effects of selective excitotoxic ablation of the LS on neuroendocrine and behavioral stress responses in rats. Bilateral ibotenic acid lesions of the LS increased hypothalamo-pituitary-adrenocortical (HPA) axis responses to forced swim stress indicated by enhanced plasma ACTH and corticosterone responses and higher stress-induced c-Fos-like immunoreactivity in the paraventricular hypothalamic nucleus. Moreover, LS-lesioned animals showed a more passive coping style in the forced swim test indicated by increased floating and reduced struggling/swimming behavior compared with sham-lesioned controls. Interestingly, intraseptal corticosteroid receptor blockade modulated behavioral stress coping but failed to change HPA axis stress responses. Further experiments aimed at elucidating underlying neurochemical mechanisms revealed that intraseptal administration of the selective 5-HT(1A) receptor antagonist WAY-100635 increased and prolonged stress-induced ACTH and corticosterone levels mimicking lesion effects, while the agonist 8-OH-DPAT suppressed HPA axis activity facilitating the inhibitory role of the LS. In addition, 8-OH-DPAT-injected animals showed increased active and decreased passive coping strategies during forced swimming suggesting antidepressant efficacy. Taken together, our data suggest that the LS promotes active stress coping behavior and is involved in a HPA-inhibitory mechanism that is at least in part mediated by septal 5-HT(1A) receptors and does not involve a glucocorticoid mediated feedback mechanism.
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“The existence of anxiolytic neurons is supported by the observation that excitotoxic LS lesions can enhance stress-induced activation of the HPA axis (Singewald et al., 2011).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Singewald et al., 2011
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Metadata
- Authors
- Singewald, G. M., Rjabokon, A., Singewald, N., & Ebner, K.
- Affiliations
- Universität Innsbruck (AT)
- Corresponding author
- Ebner, Karl
- Venue
- Neuropsychopharmacology
- Published
- 2010-12-15
- Volume
- 36
- Issue
- 4
- Pages
- 793-804
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055728
- OpenAlex
- W1987515936
- Cited by
- 149
- References
- 84
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 4 · 2022: 17 · 2021: 9 · 2020: 10 · 2019: 12 · 2018: 9 · 2017: 11 · 2016: 8 · 2015: 9 · 2014: 16 · 2013: 6 · 2012: 10
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Neuropsychopharmacology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- Austrian Science Fund
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- lateral septum, stress response, hypothalamic-pituitary-adrenal axis, forced swim test, passive coping, active coping, ACTH, corticosterone, paraventricular nucleus, c-fos, 5-HT1A receptor, 8-OH-DPAT, WAY-100635, excitotoxic lesions, antidepressant efficacy, glucocorticoid feedback
- MeSH terms
- Adaptation, Psychological, Adrenocorticotropic Hormone, Animals, Corticosterone, Male, Neurosecretory Systems, Stress, Psychological, Rats, Sprague-Dawley, Septum of Brain, Rats
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