title: OSO paradigm--A rapid behavioral screening method for acute psychosocial stress reactivity in mice.
abstract: Chronic psychosocial stress is an important environmental risk factor for the development of psychiatric diseases. However, studying the impact of chronic psychosocial stress in mice is time consuming and thus not optimally suited to 'screen' increasing numbers of genetically manipulated mouse models for psychiatric endophenotypes. Moreover, many studies focus on restraint stress, a strong physical stressor with limited relevance for psychiatric disorders. Here, we describe a simple and a rapid method based on the resident-intruder paradigm to examine acute effects of mild psychosocial stress in mice. The OSO paradigm (open field--social defeat--open field) compares behavioral consequences on locomotor activity, anxiety and curiosity before and after exposure to acute social defeat stress. We first evaluated OSO in male C57Bl/6 wildtype mice where a single episode of social defeat reduced locomotor activity, increased anxiety and diminished exploratory behavior. Subsequently, we applied the OSO paradigm to mouse models of two schizophrenia (SZ) risk genes. Transgenic mice with neuronal overexpression of Neuregulin-1 (Nrg1) type III showed increased risk-taking behavior after acute stress exposure suggesting that NRG1 dysfunction is associated with altered affective behavior. In contrast, Tcf4 transgenic mice displayed a normal stress response which is in line with the postulated predominant contribution of TCF4 to cognitive deficits of SZ. In conclusion, the OSO paradigm allows for rapid screening of selected psychosocial stress-induced behavioral endophenotypes in mouse models of psychiatric diseases.
authors.affiliation: Department of Psychiatry, Ludwig-Maximilian-University, Nussbaumstrasse 7, 80336 Munich, Germany. Electronic address: Magdalena.Brzozka@med.uni-muenchen.de.
authors.forename: M M
authors.initials: MM
authors.lastname: Brzózka
authors.affiliation: Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany; Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Electronic address: Unterbarnscheidt.Tilmann@mh-hannover.de.
authors.forename: T
authors.initials: T
authors.lastname: Unterbarnscheidt
authors.affiliation: Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany; Cellular Neurophysiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Electronic address: Schwab.Markus@mh-hannover.de.
authors.forename: M H
authors.initials: MH
authors.lastname: Schwab
authors.affiliation: Department of Psychiatry, Ludwig-Maximilian-University, Nussbaumstrasse 7, 80336 Munich, Germany; Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen, Germany. Electronic address: Moritz.Rossner@med.uni-muenchen.de.
authors.forename: M J
authors.initials: MJ
authors.lastname: Rossner
mesh_terms: D000818:Animals; D001007:Anxiety; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D001522:Behavior, Animal; D004195:Disease Models, Animal; D058068:Endophenotypes; D005106:Exploratory Behavior; D008297:Male; D051379:Mice / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D020890:Neuregulin-1 / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics; D012565:Schizophrenic Psychology; D012919:Social Behavior; D012931:Social Environment; D013315:Stress, Psychological; D000073940:Transcription Factor 4
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4
keywords: Neuregulin-1 (Nrg1); OSO paradigm; Transcription factor 4 (Tcf4); acute psychosocial stress; psychiatric endophenotypes; social defeat