Cited by 149Stress Responses and CortisolNeuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on Behavior

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The Modulatory Role of the Lateral Septum on Neuroendocrine and Behavioral Stress Responses

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Singewald, Georg M, Rjabokon, Alesja, Singewald, Nicolas, Ebner, Karl·2011·Neuropsychopharmacology

DOI 10.1038/npp.2010.213PMC PMC3055728

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Abstract

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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Authors: Singewald, G. M., Rjabokon, A., Singewald, N., & Ebner, K.
Affiliations: Universität Innsbruck (AT)
Corresponding author: Ebner, Karl
ORCID: Singewald, Nicolas
Ebner, Karl
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2010-12-15
Volume: 36
Issue: 4
Pages: 793-804
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/npp.2010.213
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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The Modulatory Role of the Lateral Septum on Neuroendocrine and Behavioral Stress Responses

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