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Titolo:
Chronic administration of the selective corticotropin-releasing factor 1 receptor antagonist CP-154,526: behavioral, endocrine and neurochemical effects in the rat
Autore:
Arborelius, L; Skelton, KH; Thrivikraman, KV; Plotsky, PM; Schulz, DW; Owens, MJ;
Indirizzi:
Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Lab Neuropsychopharmacol, Atlanta, GA 30322 USA Emory Univ Atlanta GA USA 30322 uropsychopharmacol, Atlanta, GA 30322 USA Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Lab Stress Neurobiol, Atlanta, GA USA Emory Univ Atlanta GA USA hav Sci, Lab Stress Neurobiol, Atlanta, GA USA Pfizer Inc, Pfizer Cent Res, Dept Neurosci, Groton, CT 06340 USA Pfizer Inc Groton CT USA 06340 t Res, Dept Neurosci, Groton, CT 06340 USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 2, volume: 294, anno: 2000,
pagine: 588 - 597
SICI:
0022-3565(200008)294:2<588:CAOTSC>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMPAIRED STRESS-RESPONSE; PARAVENTRICULAR NUCLEUS; MESSENGER-RNA; IMMOBILIZATION STRESS; DEFENSIVE-WITHDRAWAL; CHRONIC INFUSION; LOCUS-COERULEUS; REDUCED ANXIETY; PITUITARY; BRAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Owens, MJ Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Lab Neuropsychopharmacol, 1639 Pierce Dr,Ste 4000, Atlanta, GA 30322 USA Emory Univ 1639 Pierce Dr,Ste 4000 Atlanta GA USA 30322 0322 USA
Citazione:
L. Arborelius et al., "Chronic administration of the selective corticotropin-releasing factor 1 receptor antagonist CP-154,526: behavioral, endocrine and neurochemical effects in the rat", J PHARM EXP, 294(2), 2000, pp. 588-597

Abstract

Corticotropin-releasing factor 1 (CRF1) receptor antagonists may representa 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, aneffect 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 increasedCRF peptide and mRNA levels in the PVN of depressed patients, which may mediate the hyperactivity of the hypothalamic-pituitary-adrenal axis observedin 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/07/20 alle ore 18:09:24