Effects of the selective nonpeptide corticotropin-releasing factor receptor 1 antagonist antalarmin in the chronic mild stress model of depression in mice.
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.
Ducottet
Cecile
C
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.
Griebel
Guy
G
Belzung
Catherine
C
D000818:Animals; D003863:Depression / Q000188:drug therapy; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013315:Stress, Psychological / Q000188:drug therapy*
D005473:Fluoxetine; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D017367:Selective Serotonin Reuptake Inhibitors; C103016:antalarmin