Calcitonin gene-related peptide in the bed nucleus of the stria terminalis produces an anxiety-like pattern of behavior and increases neural activation in anxiety-related structures
Open accessAbstract
Calcitonin gene-related peptide (CGRP) evokes anxiety-like responses when infused into the lateral ventricle of rats. Because the bed nucleus of the stria terminalis (BNST) lies immediately adjacent to the lateral ventricle, is rich in CGRP receptors, and has itself been implicated in anxiety, we evaluated the hypothesis that these effects are attributable to stimulation of CGRP receptors within the BNST itself. Bilateral intra-BNST, but not dorsal, CGRP infusions (0, 200, 400, 800 ng/side) enhanced startle amplitude in a dose-dependent manner, and produced an anxiety-like response on the elevated plus maze. Intra-BNST infusion of the CGRP antagonist, αCGRP 8-37, blocked the effect of CGRP on startle, and also blocked startle potentiation produced by exposure to trimethylthiazoline (a component of fox feces that induces anxiety-like behavior in rats). Intra-BNST, but not dorsal, CGRP infusions also increased c-Fos immunoreactivity in a number of anxiety-related brain areas (central nucleus of the amygdala, locus ceruleus, ventrolateral septal nucleus, paraventricular hypothalamic nucleus, lateral hypothalamus, lateral parabrachial nucleus, dorsal raphe nucleus, and nucleus accumbens shell), all of which receive direct projections from the BNST. Together, the results indicate that the activation of BNST CGRP receptors is both necessary and sufficient for some anxiety responses and that these effects may be mediated by activation of a wider network of BNST efferent structures. If so, inhibition of CGRP receptors may be a clinically useful strategy for anxiety reduction.
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The BNST projects to hypothalamic targets that produce fear responses.
“Moreover, the BNST sends outputs to hypothalamic targets to produce fear responses (38,39)”
From Neuroanatomic differences associated with stress susceptibility and resilience (2016) · cites this paper as [39]
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Self-citation
- Authors
- Sink, K. S., Walker, D. L., Yang, Y., & Davis, M.
- Affiliations
- Emory University (US)
- Corresponding author
- Sink, Kelly S.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-02-02
- Volume
- 31
- Issue
- 5
- Pages
- 1802-1810
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3088995
- OpenAlex
- W2166310930
- Cited by
- 99
- References
- 52
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 10 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 7 · 2016: 7 · 2015: 11 · 2014: 9 · 2013: 17 · 2012: 7
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (5u19mh069056-10, MH47840)
- National Institute of Mental Health (U19-MH069056, F32MH093023, MH 47840, R37MH047840, MH069056, R01MH047840)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- calcitonin gene-related peptide, bed nucleus of the stria terminalis, anxiety-like behavior, startle potentiation, c-Fos immunoreactivity, amygdala, locus coeruleus, parabrachial nucleus, dorsal raphe nucleus, nucleus accumbens shell, hypothalamus, septal nuclei, CGRP receptor antagonism
- MeSH terms
- Calcitonin Gene-Related Peptide Receptor Antagonists, Acoustic Stimulation, Amygdala, Animals, Anxiety, Cell Count, Efferent Pathways, Hypothalamus, Immunohistochemistry, Locus Coeruleus, Male, Microinjections, Neural Pathways, Nucleus Accumbens, Paraventricular Hypothalamic Nucleus, Raphe Nuclei, Septal Nuclei, Reflex, Startle, Thiazoles, Calcitonin Gene-Related Peptide, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Receptors, Calcitonin Gene-Related Peptide, Maze Learning, Rats
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