Repeated Stimulation of CRF Receptors in the BNST of Rats Selectively Induces Social but not Panic-Like Anxiety
Open accessAbstract
Increased extra-hypothalamic corticotrophin-releasing factor (CRF) neurotransmission has been suggested as one putative factor in the pathophysiology of anxiety disorders. We have previously reported that administering repeated subanxiogenic doses (termed 'priming') of the CRF receptor agonist urocortin 1 (Ucn1) into the basolateral amygdala (BLA) of rats elicited long-lasting behavioral changes in social interaction (SI) and elevated plus maze (EPM) tests of anxiety. Although substantial similarity exists, the bed nucleus of the stria terminals (BNST) and the amygdala are thought to play distinct roles in anxiety responses. Rats primed with Ucn1 in the BLA not only demonstrated increased anxiety-like behaviors, but also physiological sensitivity to intravenous sodium lactate infusions, which is seen in subjects with panic or posttraumatic stress disorders, but not social or generalized anxiety disorders. In the present study, we tested if similar priming with subanxiogenic doses of Ucn1 in the BNST of rats will induce either chronic anxiety or sensitivity to sodium lactate. After determining the dose of Ucn1 that is subanxiogenic when injected into the BNST, repeated intra-BNST injections of this subanxiogenic dose of Ucn1 (6 fmol/100 nl) elicited persistent (present even after 4 weeks) anxiety-like responses in the SI but not EPM test. Prior local injection of a CRF receptor antagonist, astressin, into the BNST blocked this effect. Unlike Ucn1 priming in the BLA, rats primed in the BNST showed no cardiovascular changes following lactate infusion. Thus, BNST priming appears to selectively model the pathophysiology of subjects with anxiety syndromes like social anxiety, which are not lactate sensitive.
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Intra-bed nucleus of the stria terminalis CRF infusions elicit anxiety-associated behaviors in the elevated plus-maze and social interaction tests.
“intra-BNST CRF infusions have also been found to elicit anxiety-associated behaviors in the elevated plus-maze and social interaction tests (Lee et al, 2008; Sahuque et al, 2006)”
From Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety (2010) · cites this paper as Lee et al, 2008
In Experiment 2, repeated intra-BNST injections of the CRF receptor agonist Ucn1 produced anxiety-like behavior in the social interaction test but not the elevated plus-maze. The Discussion likewise reports no elevated plus-maze effect in this study and attributes that finding to Sahuque et al.; Lee et al. also infused Ucn1 rather than CRF itself. (LLM, conf=0.90)
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- Authors
- Lee, Y., Fitz, S., Johnson, P. L., & Shekhar, A.
- Affiliations
- Indiana University Indianapolis (US)
- Corresponding author
- Lee, Younglim
- Venue
- Neuropsychopharmacology
- Published
- 2008-02-20
- Volume
- 33
- Issue
- 11
- Pages
- 2586-2594
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3065211
- OpenAlex
- W1966613107
- Cited by
- 89
- References
- 61
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 8 · 2013: 11 · 2012: 11
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR001108)
- National Institute of Mental Health (R01-MH52619, MH065702, MH 052619, R01MH052619, R01MH065702, MH 52619)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- corticotropin-releasing factor, urocortin 1, bed nucleus of the stria terminalis, basolateral amygdala, anxiety, social anxiety, sodium lactate infusion, astressin, CRF receptor antagonists
- MeSH terms
- Animals, Anxiety, Corticotropin-Releasing Hormone, Male, Panic, Peptide Fragments, Septal Nuclei, Social Behavior, Rats, Wistar, Receptors, Corticotropin-Releasing Hormone, Rats, Urocortins
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