Cited by 247Stress Responses and CortisolNeuropeptides and Animal PhysiologyMemory and Neural Mechanisms

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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.

Deak, Terrence, Nguyen, Kien T., Ehrlich, Andrea L., Watkins, Linda R., Spencer, Robert L., Maier, Steven F., Licinio, Julio, Wong, Ma-Li, Chrousos, George P., Webster, Elizabeth, Gold, Philip W.·1999·Endocrinology

DOI 10.1210/endo.140.1.6415

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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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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: Nguyen, Kien T.
Watkins, Linda R.
Spencer, Robert L.
Maier, Steven F.
Wong, Ma-Li
Chrousos, George P.
Gold, Philip W.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 1999-01-01
Volume: 140
Issue: 1
Pages: 79-86
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/endo.140.1.6415
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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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.

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