title: Chronic unpredictable mild stress paradigm in male Wistar rats: effect on anxiety- and depressive-like behavior.
abstract: OBJECTIVE
  There are several models of depression. Chronic unpredictable mild stress (CMS) appears to have the greatest validity, although it is often being criticized for low reliability.
  
  
  METHODS
  Male Wistar/DV rats were used in this study to assess our modified 2-week model of CMS as a combination of psychosocial, physical and metabolic stressors and to compare the effect of acute administration of venlafaxine (VFX) and diazepam (DZP), either in stress or no stress conditions. The animals were exposed to one particular stressor each day. The time of day and duration of the stressor differed across the procedure to avoid animals to adapt to the stress stimulus. After cessation of stress, the animals underwent the following behavioral tests to assess motor activity, cognition, anxiety- and depression-like behavior: Open field test, Elevated plus maze, Forced swim test, Stress-iduced hyperthermia, Light/dark test and Y maze. To assess hypothalamic-pituitary-adrenal axis (HPA) reactivity in our CMS model, plasma corticosterone levels were measured 24 h after termination of stress.
  
  
  RESULTS
  Corticosterone levels were significantly increased compared to control values (p<0.05) in our experimental schedule of CMS. Our paradigm produced delayed anxiety-like behavior observed in Open field (decreased time spent in central zone 3 weeks after CMS, p<0.05), with anxiolytic effect of CMS shortly after its cessation. Stressed animals spent more time in the open arms of Elevated plus maze (p<0.05) and travelled longer distance in the light zone of the Light/dark box (p<0.01). CMS did not increase the behavioral despair analyzed in Forced swim test yet it disrupted the capacity of the Stress-induced hyperthermia test (CMS rats failed to react to the stress by increasing the core temperature).
  
  
  CONCLUSIONS
  Based on our results, we can conclude that our CMS protocol leads to increased corticosterone levels as a result of HPA axis hyperactivity and produces delayed onset of anxiogenic behavior. Moreover, CMS exerted a substantial effect on the behavioral outputs, interfering with drug testing.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic.|Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic.
authors.forename: Romana
authors.initials: R
authors.lastname: Koprdova
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Eszter
authors.initials: E
authors.lastname: Bögi
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic.|Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic.
authors.forename: Kristína
authors.initials: K
authors.lastname: Belovičová
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Natália
authors.initials: N
authors.lastname: Sedláčková
authors.affiliation: Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovak Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Okuliarová
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Eduard
authors.initials: E
authors.lastname: Ujházy
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Mojmír
authors.initials: M
authors.lastname: Mach
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology*; D003345:Corticosterone / Q000097:blood*; D003863:Depression / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology*
chemical_list: D003345:Corticosterone