Antidepressant-like effects of CRF1 receptor antagonist SSR125543 in an animal model of depression.
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.
Department of Psychiatry, Center for Alcohol Studies, CB #7178, 3009 Thurston-Bowles Bldg., University of North Carolina, Chapel Hill, NC 27599-7178, USA. dhover@med.unc.edu
David H
DH
Overstreet
Guy
G
Griebel
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy* / Q000235:genetics; D003891:Desipramine / Q000494:pharmacology / Q000627:therapeutic use; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D012919:Social Behavior; D013550:Swimming; D013843:Thiazines / Q000494:pharmacology / Q000627:therapeutic use*; D000099052:CRF Receptor, Type 1
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D006846:Hydrocarbons, Halogenated; D018019:Receptors, Corticotropin-Releasing Hormone; C502407:SSR125543; D012702:Serotonin Antagonists; D013843:Thiazines; D005473:Fluoxetine; D000099052:CRF Receptor, Type 1; D003891:Desipramine