The Effect of Lateral Septum Corticotropin-Releasing Factor Receptor 2 Activation on Anxiety Is Modulated by Stress

Henry, Brook; Vale, Wylie; Markou, Athina

doi:10.1523/jneurosci.1494-06.2006

Cited by 147Neuropeptides and Animal PhysiologyStress Responses and CortisolNeurotransmitter Receptor Influence on Behavior

The Effect of Lateral Septum Corticotropin-Releasing Factor Receptor 2 Activation on Anxiety Is Modulated by Stress

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Henry, Brook, Vale, Wylie, Markou, Athina·2006·The Journal of Neuroscience

DOI 10.1523/jneurosci.1494-06.2006PMC PMC6674509

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Abstract

Corticotropin-releasing factor (CRF), a 41 amino acid peptide, mediates endocrine, autonomic, and behavioral responses to stress. Whereas the CRF 1 receptor appears to contribute to anxiety associated with stress, the role of the CRF 2 receptor remains unclear and may depend on drug dose, brain location, or testing environment. Results involving treatments with selective CRF 2 receptor agonists or antagonists and the behavior of CRF 2 receptor knock-out mice suggest both anxiogenic and anxiolytic effects of CRF 2 receptor activation. The present study tested the hypothesis that the effect of CRF 2 receptor activation on anxiety depends on the stress level of the animal. The selective CRF 2 receptor agonist urocortin 2 was infused into the lateral septum of mice under low- or high-stress (30 min of immobilization) testing conditions, and then behavior in the light–dark box, open-field, and novel-object tests was assessed. In the low-stress environment, 240 pmol of septal urocortin 2 increased anxiety, but lower doses (0.48, 4.8, and 48 pmol) did not have consistent effects. However, in the high-stress condition, 48 pmol of septal urocortin 2 significantly increased anxiety compared with control in wild-type but not CRF 2 receptor knock-out mice in the light–dark box. Septal administration of the relatively selective CRF 2 antagonist astressin-2B, but not the CRF 1- selective antagonist antalarmin, blocked the anxiogenic effects of urocortin 2. Urocortin 2 infusion into the medial septum or lateral ventricle did not affect anxiety measures. These results indicate that the effect of septal CRF 2 receptor activation on anxiety is dependent on stress level.

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CRFR activation in the lateral septum increases anxiety-related phenotypes by way of activation of CRFR type 2-expressing GABAergic projection neurons residing there.
“Corticotropin releasing factor receptor (CRFR) activation in the lateral septum increases anxiety-related phenotypes96 by way of activation of CRFR type 2–expressing GABAergic projection neurons residing there97.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [96]
LS injections of agonists of the type 2 corticotropin-releasing factor receptor (Crfr2) have resulted in increased anxiety.
“For example, LS injections of agonists of the type 2 corticotropin-releasing factor receptor (Crfr2) have resulted in increased anxiety (Radulovic et al., 1999; Bakshi et al., 2002; Henry et al., 2006).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Henry et al., 2006
The light-dark box, open field, and novel object tests are sensitive to modulation of LS Crfr2+ neuronal function.
“these tests were chosen as pharmacological experiments showed them to be sensitive to modulation of LS Crfr2+ neuronal function (Henry et al., 2006).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Henry et al., 2006
Anxiogenic cell populations in the lateral septum were inferred to act by providing local inhibition on anxiolytic output.
“Anxiogenic cell populations in the LS were, therefore, inferred to act by providing local inhibition on such anxiolytic output (Henry et al., 2006).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Henry et al., 2006

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The effect of lateral septum CRF₂ receptor activation on anxiety is modulated by stress
Henry, B. L. (2006) · eScholarship (California Digital Library)
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The localization of brain sites of anxiogenic-like effects of urocortin-2
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Self-citation

Authors: Henry, B., Vale, W., & Markou, A.
Affiliations: Scripps Research Institute (US)
Salk Institute for Biological Studies (US)
Corresponding author: Markou, Athina
ORCID: Vale, Wylie
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2006-09-06
Volume: 26
Issue: 36
Pages: 9142-9152
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.1494-06.2006
PMC: PMC6674509
OpenAlex: W1996743601
Cited by: 147
References: 38
Citations by year: 2026: 5 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 5 · 2021: 8 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 8 · 2016: 7 · 2015: 5 · 2014: 11 · 2013: 3 · 2012: 10
FWCI: 5.57
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 181 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Mental Health (U01 MH 69062, R01MH62527, U01MH069062, R01MH062527)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 26741, P01DK026741)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: corticotropin-releasing factor, CRF2 receptor, urocortin 2, antalarmin, lateral septum, anxiety, stress levels, restraint stress, CRF1 receptor, medial septum, dose dependence
MeSH terms: CRF Receptor, Type 1, Animals, Anxiety, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Injections, Intraventricular, Male, Mice, Inbred ICR, Stress, Psychological, Receptors, Corticotropin-Releasing Hormone, Mice, Knockout, Septum of Brain, Mice, Urocortins

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The Effect of Lateral Septum Corticotropin-Releasing Factor Receptor 2 Activation on Anxiety Is Modulated by Stress

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