The anxiolytic effect of the CRH 1 receptor antagonist R121919 depends on innate emotionality in rats

The anxiolytic effect of the CRH 1 receptor antagonist R121919 depends on innate emotionality in... Hyperactivity of central corticotropin‐releasing hormone (CRH) circuits appears to contribute to the symptomatology of affective and anxiety disorders and therefore CRH receptor antagonists have attracted attention as potential therapeutic agents. R121919, a novel high‐affinity nonpeptide CRH1 receptor antagonist, displaced 125I‐oCRH in rat pituitary, cortex and amygdala, but not in choroid plexus or cerebral blood vessels in vitro and in vivo, which is consistent with CRH1 receptor antagonism. In vivo, R121919 significantly inhibited stress‐induced corticotropin release in rats selectively bred for high‐ and low‐anxiety‐related behaviour but displayed anxiolytic effects in high‐anxiety rats only. These data, corroborated by ex vivo receptor occupancy studies, suggest that this animal model is appropriate for the evaluation of CRH1 receptor antagonists and that compounds such as R121919 will be beneficial whenever the central stress hormone system is hyperactive. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

The anxiolytic effect of the CRH 1 receptor antagonist R121919 depends on innate emotionality in rats

Loading next page...
 
/lp/wiley/the-anxiolytic-effect-of-the-crh-1-receptor-antagonist-r121919-depends-0R8iJnG6w2
Publisher
Wiley
Copyright
Copyright © 2001 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
DOI
10.1046/j.0953-816X.2000.01383.x
Publisher site
See Article on Publisher Site

Abstract

Hyperactivity of central corticotropin‐releasing hormone (CRH) circuits appears to contribute to the symptomatology of affective and anxiety disorders and therefore CRH receptor antagonists have attracted attention as potential therapeutic agents. R121919, a novel high‐affinity nonpeptide CRH1 receptor antagonist, displaced 125I‐oCRH in rat pituitary, cortex and amygdala, but not in choroid plexus or cerebral blood vessels in vitro and in vivo, which is consistent with CRH1 receptor antagonism. In vivo, R121919 significantly inhibited stress‐induced corticotropin release in rats selectively bred for high‐ and low‐anxiety‐related behaviour but displayed anxiolytic effects in high‐anxiety rats only. These data, corroborated by ex vivo receptor occupancy studies, suggest that this animal model is appropriate for the evaluation of CRH1 receptor antagonists and that compounds such as R121919 will be beneficial whenever the central stress hormone system is hyperactive.

Journal

European Journal of NeuroscienceWiley

Published: Jan 1, 2001

References

  • Characterization of the behavioral profile of the non‐peptide CRF receptor antagonist CP‐154,526 in anxiety models in rodents
    Griebel, Griebel; Perrault, Perrault; Sanger, Sanger
  • The rationale for corticotropin‐releasing hormone receptor (CRH‐R) antagonists to treat depression and anxiety
    Holsboer, Holsboer
  • Chronic infusion of a CRH 1 receptor antisense oligodeoxynucleotide into the central nucleus of the amygdala reduced anxiety‐related behavior in socially defeated rats
    Liebsch, Liebsch; Landgraf, Landgraf; Gerstberger, Gerstberger; Probst, Probst; Wotjak, Wotjak; Engelmann, Engelmann; Holsboer, Holsboer; Montkowski, Montkowski
  • Behavioural profiles of two Wistar rat lines selectively bred for high or low anxiety‐related behaviour
    Liebsch, Liebsch; Montkowski, Montkowski; Holsboer, Holsboer; Landgraf, Landgraf
  • Effects of the high‐affinity corticotropin‐releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients
    Zobel, Zobel; Nickel, Nickel; Künzel, Künzel; Ackl, Ackl; Sonntag, Sonntag; Ising, Ising; Holsboer, Holsboer

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off