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The Impact of the Nonpeptide Corticotropin-Releasing Hormone Antagonist Antalarmin on Behavioral and Endocrine Responses to Stress**This research was supported by NIMH Grant MH-50479 and the Undergraduate Research Opportunities Program at the University of Colorado at Boulder.
Abstract
The nonpeptide CRH antagonist antalarmin has been shown to block both behavioral and endocrine responses to CRH. However, it's potential activity in blunting behavioral and endocrine sequelae of stressor exposure has not been assessed. Because antagonism of central CRH by alpha-helical CRH attenuates conditioned fear responses, we sought to test antalarmin in this regard. In addition, it remains unclear as to whether this is a result of receptor blockade during conditioning or during testing. Thus, we explored whether CRH mediates the induction or expression of conditioned fear (freezing in a context previously associated with 2 footshocks; 1.0 mA, 5 sec each). Furthermore, because rats previously exposed to inescapable shock (IS; 100 shocks, 1.6 mA, 5 sec each), demonstrate enhanced fear conditioning, we investigated whether this effect would be blocked by antalarmin. Antalarmin (20 mg/kg x 2 ml i.p.) impaired both the induction and expression of conditioned fear. In addition, antalarmin blocked the enhancement of fear conditioning produced by prior exposure to IS. Despite the marked behavioral effects observed in antalarmin-treated rats, antalarmin had no effect on IS-induced rises in ACTH or corticosterone. However, antalarmin did block the ACTH response produced by exposure to 2 footshocks.
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“There is also evidence that CRF is involved in context conditioning.”
From Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety (2010) · cites this paper as Deak et al, 1999
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Metadata
- Authors
- Deak, T., Nguyen, K. T., Ehrlich, A. L., Watkins, L. R., Spencer, R. L., Maier, S. F., Licinio, J., Wong, M.-L., Chrousos, G. P., Webster, E., & Gold, P. W.
- Affiliations
- Department of Psychology (T.D., K.T.N., A.L.E., L.R.W., R.L.S., S.F.M.), University of Colorado, Boulder, Colorado 80309-0345;
- University of Colorado Boulder (US)
- Clinical Neuroendocrinology Branch (J.L., M.-L.W., P.W.G.), National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1284;
- National Institutes of Health (US)
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1999-01-01
- Volume
- 140
- Issue
- 1
- Pages
- 79-86
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2149878393
- Cited by
- 242
- References
- 59
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 4 · 2021: 2 · 2020: 5 · 2019: 7 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 9 · 2013: 5 · 2012: 8
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH 50479)
- 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
- antalarmin, corticotropin-releasing factor, fear conditioning, freezing behavior, inescapable shock, stress, ACTH, corticosterone, stress response
- MeSH terms
- Adrenal Cortex Hormones, Adrenocorticotropic Hormone, Animals, Behavior, Animal, Conditioning, Operant, Corticotropin-Releasing Hormone, Electroshock, Escape Reaction, Fear, Male, Pituitary-Adrenal System, Pyrimidines, Pyrroles, Stress, Physiological, Rats, Sprague-Dawley, Receptors, Corticotropin-Releasing Hormone, Rats
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