title: Forebrain-specific trkB-receptor knockout mice: behaviorally more hyperactive than "depressive".
abstract: BACKGROUND
  According to the neurotrophin hypothesis of depression, decreased activity of brain-derived neurotrophic factor (BDNF) contributes to behavioral and plasticity-related alterations in depressed patients. We investigated the hypothesis that mice with a forebrain-specific knockout of the trkB receptor, the main mediator of BDNF signaling, represent a genetic animal model for depression.
  
  
  METHODS
  Using the CRE-loxP system, we bred trkB(CaMKII-CRE) mice with a trkB-receptor disruption in the forebrain. We subjected trkB-mutant mice to a battery of behavioral tests, comprising open field, elevated zero maze, emergence test, novel object test, and forced swim. Additionally, we investigated the hypothalamic-pituitary-adrenal (HPA) axis immunohistochemically and by plasma analyses.
  
  
  RESULTS
  trkB(CaMKII-CRE) mice showed a stereotyped hyper-locomotion with reduced explorative activity, and impulsive reactions to novel stimuli. The trkB-mutant mice did not exhibit depressionlike behaviors such as increased "despair" in the forced swim test, increased anxiety in the elevated zero maze, or neophobia in the novel object test. Furthermore, no HPA dysregulation was observed under normal and stressful conditions.
  
  
  CONCLUSIONS
  trkB(CaMKII-CRE) mice cannot be regarded as a genetic mouse model of depression. Instead, the behavioral symptoms of trkB(CaMKII-CRE) mice, comprising hyper-locomotion, stereotyped behaviors, and cognitive impairments, are similar to those postulated for mouse models of attention-deficit disorder.
authors: Central Institute of Mental Health Mannheim, University of Heidelberg, Heidelberg, Germany.
authors: Björn
authors: B
authors: Zörner
authors: David P
authors: DP
authors: Wolfer
authors: Dorothee
authors: D
authors: Brandis
authors: Oliver
authors: O
authors: Kretz
authors: Christiane
authors: C
authors: Zacher
authors: Rime
authors: R
authors: Madani
authors: Ilona
authors: I
authors: Grunwald
authors: Hans-Peter
authors: HP
authors: Lipp
authors: Rüdiger
authors: R
authors: Klein
authors: Fritz A
authors: FA
authors: Henn
authors: Peter
authors: P
authors: Gass
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003863:Depression / Q000378:metabolism / Q000503:physiopathology*; D005106:Exploratory Behavior; D007150:Immunohistochemistry; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009068:Movement; D016548:Prosencephalon / Q000033:anatomy & histology / Q000378:metabolism* / Q000503:physiopathology; D011595:Psychomotor Agitation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D011930:Reaction Time; D020813:Receptor, trkB / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013239:Stereotyped Behavior; D013550:Swimming; D013997:Time Factors
chemical_list: D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D020813:Receptor, trkB; D003345:Corticosterone