Antidepressant-like effects of CRF1 receptor antagonist SSR125543 in an animal model of depression.

Full Abstract

Much interest has been expressed in the antidepressant potential of nonpeptide, orally active corticotropin-releasing factor (CRF) receptor antagonists in recent years. Therefore, the present investigation examined the antidepressant-like effects of the novel CRF(1) receptor antagonist SSR125543 on the exaggerated swim test immobility in the Flinders Sensitive Line rat, a genetic animal model of depression. Chronic treatment with SSR125543 (3, 10, 20, 30 mg/kg, i.p.) for 14 days significantly increased swimming in the Flinders Sensitive Line rats. The reference serotonin reuptake inhibitor fluoxetine (5 mg/kg, i.p.) and the tricyclic antidepressant desipramine (5 mg/kg, i.p.) also significantly increased swimming, as expected. The higher doses of SSR125543 (20 and 30 mg/kg) also significantly increased the abnormally low level of social interaction behavior in the Flinders Sensitive Line rats. Together, these findings indicate that the CRF(1) receptor antagonist SSR125543 has both antidepressant- and anxiolytic-like effects in the Flinders Sensitive Line rats.

Author information

Author/s: Overstreet, David H (DH); Griebel, Guy (G);

Affiliation: Department of Psychiatry, Center for Alcohol Studies, CB #7178, 3009 Thurston-Bowles Bldg., University of North Carolina, Chapel Hill, NC 27599-7178, USA. dhover(-atsign-)med.unc.edu

Journal and publication information

Publication Type: Comparative Study; Journal Article

Journal: European journal of pharmacology (Eur J Pharmacol), published in Netherlands. (Language: eng)

Reference: 2004-Aug; vol 497 (issue 1) : pp 49-53

Dates: Created 2004/08/23; Completed 2005/08/01; Revised 2006/11/15;

PMID: 15321734, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals
Anti-Anxiety Agents - pharmacology; therapeutic use
Antidepressive Agents - pharmacology; therapeutic use
Antidepressive Agents, Tricyclic - pharmacology
Depression - drug therapy; genetics
Desipramine - pharmacology; therapeutic use
Fluoxetine - pharmacology; therapeutic use
Hydrocarbons, Halogenated - pharmacology; therapeutic use

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Anti-Anxiety Agents (0) ; Antidepressive Agents (0) ; Antidepressive Agents, Tricyclic (0) ; CRF receptor type 1 (0) ; Hydrocarbons, Halogenated (0) ; Receptors, Corticotropin-Releasing Hormone (0) ; SSR125543 (0) ; Serotonin Antagonists (0) ; Thiazines (0) ; Desipramine (50-47-5) ; Fluoxetine (54910-89-3)

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