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Effects of the selective nonpeptide corticotropin-releasing factor receptor 1 antagonist antalarmin in the chronic mild stress model of depression in mice.

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EA 3248 Psychobiologie des émotions, IFR120 Imagerie et exploration fonctionnelles, Faculte des Sciences and Techniques, UFR Sciences et techniques, Universite Francois Rabelais, Parc de Grandmont Avenue Monge, F-37200, Tours, France.


Several recent studies on corticotropin-releasing factor (CRF) have suggested that this neuropeptide may play a role in depression. Consequently, CRF receptor antagonists have been proposed as potential new agents for the treatment of this condition. This study investigated the effects of a 4-week treatment with the well-known CRF(1) receptor antagonist, antalarmin, and the prototypical selective serotonin reuptake inhibitor (SSRI), fluoxetine, in the chronic mild stress (CMS) model in BALB/c mice. Animals were exposed to 9 weeks of CMS which rapidly (within 2 weeks) produced decrease of physical state (PS), body weight gain and blunted emotional response in the light/dark test. Chronic treatment with antalarmin (10 mg/kg ip) and fluoxetine (10 mg/kg ip) led to an improvement of CMS-induced modifications. These results suggest that CRF(1) receptor antagonists may represent potential antidepressants.

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