Antagonism of CRF2 receptors produces anxiolytic behavior in animal models of anxiety

Takahashi, Lorey K; Ho, Siew Peng; Livanov, Valentin; Graciani, Nilsa; Arneric, Stephen P

doi:10.1016/s0006-8993(01)02405-2

Cited by 132Neuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on BehaviorRegulation of Appetite and Obesity

Antagonism of CRF2 receptors produces anxiolytic behavior in animal models of anxiety

Takahashi, Lorey K, Ho, Siew Peng, Livanov, Valentin, Graciani, Nilsa, Arneric, Stephen P·2001·Brain Research

DOI 10.1016/s0006-8993(01)02405-2

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Abstract

Two pharmacologically distinct CRF receptors are distributed in different brain regions and peripheral tissues. Studies suggest that CRF(1) receptors play an important role in mediating the anxiety provoking effects of CRF. In contrast, far less functional information is available on CRF(2) receptors. Therefore, we conducted dose response studies using antisauvagine-30 (anti-SVG-30, 0-20 microg, 20-min pretreatment, i.c.v.), a potent CRF(2) peptide antagonist, and tested rats in three models of anxiety - the conditioned freezing, the elevated plus maze, and the defensive-withdrawal test. Anti-SVG-30 produced a significant dose-dependent reduction in conditioned freezing. In the elevated plus maze test, administration of anti-SVG-30 effectively increased the number of entries and time spent in the open arms. In the defensive-withdrawal test, anti-SVG-30 treatment facilitated exploratory activity in a large illuminated open field. Thus, in all three animal models, administration of anti-SVG-30 was consistent in producing an anxiolytic-like behavioral effect. In addition, a dose of anti-SVG-30 (10 microg) that produced anxiolytic-like behavior had no significant effects on locomotor activity measured in an automated activity box. This latter finding suggests that antagonism of CRF(2) receptors is not associated with a non-specific increase in behavioral movements. These results provide evidence that, in addition to CRF(1) receptors, CRF(2) receptors may play an important role in the mediation of anxiety behavior.

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CRF-R1 activation mediates many stress effects in rats; CRF-R2 activation can be the same, opposing, or ineffective depending on assay and brain region.
“CRF-R1 activation mediates many of these stress effects in rats, while CRF-R2 activation is alternately the same as CRF-R1, opposing CRF-R1, or ineffective in modulating stress, depending on the assay and the brain region (Ho et al 2001; Takahashi et al 2001; Valdez et al 2004; Zhao et al 2007; for a review see Heinrichs and Koob, 2004).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Takahashi et al 2001

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Authors: Takahashi, L. K., Ho, S. P., Livanov, V., Graciani, N., & Arneric, S. P.
Affiliations: University of Hawaiʻi at Mānoa (US)
DuPont (United States) (US)
Corresponding author: Takahashi, Lorey K
Venue: Brain Research
Publisher: Elsevier BV
Published: 2001-06
Volume: 902
Issue: 2
Pages: 135-142
ISSN: 0006-8993 (ISSN-L)
DOI: 10.1016/s0006-8993(01)02405-2
OpenAlex: W2065241960
Cited by: 132
References: 56
Citations by year: 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 7 · 2013: 5 · 2012: 2
FWCI: 4.75
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Brain Research (publishedVersion)
PubMed (publishedVersion)
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 › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: CRF2 receptor, corticotropin-releasing factor, anxiolytic behavior, CRF receptor antagonists, conditioned freezing, elevated plus maze, locomotor activity, anxiety models, rats
MeSH terms: Animals, Anxiety, Behavior, Animal, Brain, Conditioning, Psychological, Corticotropin-Releasing Hormone, Disease Models, Animal, Dose-Response Relationship, Drug, Fear, Male, Motor Activity, Neurons, Peptide Fragments, Stress, Physiological, Rats, Sprague-Dawley, Receptors, Corticotropin-Releasing Hormone, Maze Learning, Rats

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Antagonism of CRF2 receptors produces anxiolytic behavior in animal models of anxiety

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