PMID- 14625139
OWN - NLM
STAT- MEDLINE
DCOM- 20031229
LR  - 20190815
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 54
IP  - 10
DP  - 2003 Nov 15
TI  - Forebrain-specific trkB-receptor knockout mice: behaviorally more hyperactive 
      than "depressive".
PG  - 972-82
AB  - 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.
FAU - Zorner, Bjorn
AU  - Zorner B
AD  - Central Institute of Mental Health Mannheim, University of Heidelberg, 
      Heidelberg, Germany.
FAU - Wolfer, David P
AU  - Wolfer DP
FAU - Brandis, Dorothee
AU  - Brandis D
FAU - Kretz, Oliver
AU  - Kretz O
FAU - Zacher, Christiane
AU  - Zacher C
FAU - Madani, Rime
AU  - Madani R
FAU - Grunwald, Ilona
AU  - Grunwald I
FAU - Lipp, Hans-Peter
AU  - Lipp HP
FAU - Klein, Rudiger
AU  - Klein R
FAU - Henn, Fritz A
AU  - Henn FA
FAU - Gass, Peter
AU  - Gass P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Adrenocorticotropic Hormone/blood
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Animal
MH  - Corticosterone/blood
MH  - Corticotropin-Releasing Hormone/metabolism
MH  - Depression/metabolism/*physiopathology
MH  - Exploratory Behavior
MH  - Immunohistochemistry
MH  - Maze Learning
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Movement
MH  - Prosencephalon/anatomy & histology/*metabolism/physiopathology
MH  - Psychomotor Agitation/genetics/metabolism/*physiopathology
MH  - Reaction Time
MH  - Receptor, trkB/deficiency/genetics/*metabolism
MH  - Stereotyped Behavior
MH  - Swimming
MH  - Time Factors
EDAT- 2003/11/20 05:00
MHDA- 2003/12/31 05:00
CRDT- 2003/11/20 05:00
PHST- 2003/11/20 05:00 [pubmed]
PHST- 2003/12/31 05:00 [medline]
PHST- 2003/11/20 05:00 [entrez]
AID - S0006322303004189 [pii]
AID - 10.1016/s0006-3223(03)00418-9 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2003 Nov 15;54(10):972-82. doi: 10.1016/s0006-3223(03)00418-9.