title: The acute social defeat stress and nest-building test paradigm: A potential new method to screen drugs for depressive-like symptoms.
abstract: Psychosocial stress can cause mental conditions such as depression in humans. To develop drug therapies for the treatment of depression, it is necessary to use animal models of depression to screen drug candidates that exhibit anti-depressive effects. Unfortunately, the present methods of drug screening for antidepressants, the forced-swim test and tail-suspension test, are limiting factors in drug discovery because they are not based on the constructive validity of objective phenotypes in depression. Previously, we discovered that the onset of nest building is severely delayed in mice exposed to subchronic mild social defeat stress (sCSDS). Therefore, a novel paradigm combining acute social defeat stress (ASDS) and the nest-building test (SNB) were established for the efficient screening of drugs for depressive-like symptoms. Since ASDS severely delayed the nest-building process as shown in chronically social defeated mice, we sought to rescue the delayed nest-building behavior in ASDS mice. Injecting a specific serotonin 2a receptor antagonist (SR-46349B), the nest-building deficit exhibited by ASDS mice was partially rescued. On the other hand, a selective serotonin reuptake inhibitor (fluoxetine) did not rescue the nest-building deficit in ASDS mice. Therefore, we conclude that the SNB paradigm is an another potential behavioral method for screening drugs for depressive-like symptoms including attention deficit, anxiety, low locomotion, and decreased motivation.
authors.affiliation: College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan.
authors.forename: Hikari
authors.initials: H
authors.lastname: Otabi
authors.affiliation: College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan; Ibaraki University Cooperation between Agriculture and Medical Science (IUCAM), Ami, Ibaraki 300-0393, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Goto
authors.affiliation: College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan; Ibaraki University Cooperation between Agriculture and Medical Science (IUCAM), Ami, Ibaraki 300-0393, Japan; United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu-city, Tokyo 183-8509, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Okayama
authors.affiliation: College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan; Ibaraki University Cooperation between Agriculture and Medical Science (IUCAM), Ami, Ibaraki 300-0393, Japan; United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu-city, Tokyo 183-8509, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kohari
authors.affiliation: College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan; Ibaraki University Cooperation between Agriculture and Medical Science (IUCAM), Ami, Ibaraki 300-0393, Japan; United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu-city, Tokyo 183-8509, Japan. Electronic address: atsushi.toyoda.0516@vc.ibaraki.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Toyoda
mesh_terms: D000818:Animals; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004291:Dominance-Subordination; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000494:pharmacology; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009425:Nesting Behavior / Q000187:drug effects*; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013315:Stress, Psychological / Q000188:drug therapy*
chemical_list: D005464:Fluorobenzenes; D005473:Fluoxetine; D010636:Phenols; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C076033:SR 46349B
keywords: Behavior; Depression; Nest building; Social defeat