JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Arborelius, L.
Right arrow Articles by Owens, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arborelius, L.
Right arrow Articles by Owens, M. J.

Vol. 294, Issue 2, 588-597, August 2000

Chronic Administration of the Selective Corticotropin-Releasing Factor 1 Receptor Antagonist CP-154,526: Behavioral, Endocrine and Neurochemical Effects in the Rat1

Lotta Arborelius, Kelly H. Skelton, Karacheri V. Thrivikraman, Paul M. Plotsky, David W. Schulz and Michael J. Owens

Laboratories of Neuropsychopharmacology (L.A., K.H.S., M.J.O.) and Stress Neurobiology (K.V.T., P.M.P.), Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia; and the Department of Neuroscience (D.W.S.), Pfizer Central Research, Groton, Connecticut

Corticotropin-releasing factor 1 (CRF1) receptor antagonists may represent a novel group of drugs for the pharmacotherapy of depression and/or anxiety disorders. We have investigated the behavioral, endocrine, and neurochemical effects of chronic administration of a selective CRF1 receptor antagonist, CP-154,526. After 9 to 10 days of treatment with CP-154,526 (3.2 mg/kg/day), defensive withdrawal behavior was significantly decreased suggesting anxiolytic activity. In animals treated for 14 days with the low dose of CP-154,526, serum corticosterone concentrations returned to baseline levels faster after application of an airpuff startle. Using in situ hybridization, no changes in CRF1 receptor mRNA expression were detected in parietal cortex, basolateral amygdala, or cerebellum after chronic treatment with CP-154,526. A dose-dependent decrease in CRF mRNA expression was observed in the hypothalamic paraventricular nucleus (PVN) and the Barrington's nucleus, an effect that was significant at the high but not the low dose of CP-154,526. CP-154,526 did not alter central CRF2A receptor binding or mRNA expression, or urocortin mRNA expression. The present findings suggest that chronic administration of CP-154,526 produces anxiolytic-like effects but no evidence of adrenal insufficiency. Previous postmortem studies revealed increased CRF peptide and mRNA levels in the PVN of depressed patients, which may mediate the hyperactivity of the hypothalamic-pituitary-adrenal axis observed in such patients. In view of a possible use for CRF1 receptor antagonists in the treatment of depression, the present finding that CP-154,526 decreases CRF synthesis in the PVN is of considerable interest.

1 Supported by a grant from Pfizer Incorporated, the Swedish Medical Research Council, and the Svenska Institutet.

0022-3565/00/2942-0588$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Pastor, C. S. McKinnon, A. C. Scibelli, S. Burkhart-Kasch, C. Reed, A. E. Ryabinin, S. C. Coste, M. P. Stenzel-Poore, and T. J. Phillips
From the Cover: Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin1-independent mechanism
PNAS, July 1, 2008; 105(26): 9070 - 9075.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. Le, J. A. Gruner, J. R. Mathiasen, M. J. Marino, and H. Schaffhauser
Correlation between ex Vivo Receptor Occupancy and Wake-Promoting Activity of Selective H3 Receptor Antagonists
J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 902 - 909.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Larauche, S. Bradesi, M. Million, P. McLean, Y. Tache, E. A. Mayer, and J. A. McRoberts
Corticotropin-releasing factor type 1 receptors mediate the visceral hyperalgesia induced by repeated psychological stress in rats
Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G1033 - G1040.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
C. Doyon, P. Samson, J. Lalonde, and D. Richard
Effects of the CRF1 receptor antagonist SSR125543 on energy balance and food deprivation-induced neuronal activation in obese Zucker rats
J. Endocrinol., April 1, 2007; 193(1): 11 - 19.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. R. Ayala, J. Pushkas, J. D. Higley, D. Ronsaville, P. W. Gold, G. P. Chrousos, K. Pacak, K. A. Calis, M. Gerald, S. Lindell, et al.
Behavioral, Adrenal, and Sympathetic Responses to Long-Term Administration of an Oral Corticotropin-Releasing Hormone Receptor Antagonist in a Primate Stress Paradigm
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5729 - 5737.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. Chen, J. Vaughan, and W. W. Vale
Glucocorticoids Regulate the Expression of the Mouse Urocortin II Gene: A Putative Connection between the Corticotropin-Releasing Factor Receptor Pathways
Mol. Endocrinol., August 1, 2003; 17(8): 1622 - 1639.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
Y.-W. Li, G. Hill, H. Wong, N. Kelly, K. Ward, M. Pierdomenico, S. Ren, P. Gilligan, S. Grossman, G. Trainor, et al.
Receptor Occupancy of Nonpeptide Corticotropin-Releasing Factor 1 Antagonist DMP696: Correlation with Drug Exposure and Anxiolytic Efficacy
J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 86 - 96.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. A. Gutman, M. J. Owens, K. H. Skelton, K. V. Thrivikraman, and C. B. Nemeroff
The Corticotropin-Releasing Factor1 Receptor Antagonist R121919 Attenuates the Behavioral and Endocrine Responses to Stress
J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 874 - 880.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. A. Pelleymounter, M. Joppa, N. Ling, and A. C. Foster
Pharmacological Evidence Supporting a Role for Central Corticotropin-Releasing Factor2 Receptors in Behavioral, but not Endocrine, Response to Environmental Stress
J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 145 - 152.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. Gully, M. Geslin, L. Serva, E. Fontaine, P. Roger, C. Lair, V. Darre, C. Marcy, P.-E. Rouby, J. Simiand, et al.
4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine Hydrochloride (SSR125543A): A Potent and Selective Corticotrophin-Releasing Factor1 Receptor Antagonist. I. Biochemical and Pharmacological Characterization
J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 322 - 332.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
G. Griebel, J. Simiand, R. Steinberg, M. Jung, D. Gully, P. Roger, M. Geslin, B. Scatton, J.-P. Maffrand, and P. Soubrie
4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1, 3-thiazol-2-amine Hydrochloride (SSR125543A), a Potent and Selective Corticotrophin-Releasing Factor1 Receptor Antagonist. II. Characterization in Rodent Models of Stress-Related Disorders
J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 333 - 345.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
C. Keller, A. Bruelisauer, M. Lemaire, and A. Enz
Brain Pharmacokinetics of a Nonpeptidic Corticotropin-Releasing Factor Receptor Antagonist
Drug Metab. Dispos., February 1, 2002; 30(2): 173 - 176.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2000 by the American Society for Pharmacology and Experimental Therapeutics.