Zorner, B., Wolfer, D. P., Brandis, D., Kretz, O., Zacher, C., Madani, R., Grunwald, I., Lipp, H. P., Klein, R., Henn, F. A., Gass, P. (November 2003) Forebrain-specific trkB-receptor knockout mice: behaviorally more hyperactive than "depressive". Biol Psychiatry, 54 (10). pp. 972-82. ISSN 0006-3223 (Print)0006-3223 (Linking)
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Adrenocorticotropic Hormone/blood Analysis of Variance Animals Behavior, Animal Corticosterone/blood Corticotropin-Releasing Hormone/metabolism Depression/metabolism/ physiopathology Exploratory Behavior Immunohistochemistry Maze Learning Mice Mice, Inbred C57BL Mice, Transgenic Movement Prosencephalon/anatomy & histology/ metabolism/physiopathology Psychomotor Agitation/genetics/metabolism/ physiopathology Reaction Time Receptor, trkB/deficiency/genetics/ metabolism Stereotyped Behavior Swimming Time Factors |
| Subjects: | diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics diseases & disorders > mental disorders diseases & disorders > mental disorders > mood disorders organism description > animal diseases & disorders > mental disorders > mood disorders > depression organs, tissues, organelles, cell types and functions > tissues types and functions > forebrain organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > tissues types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transgenic animal |
| CSHL Authors: | |
| Communities: | CSHL labs > Henn lab |
| Depositing User: | Matt Covey |
| Date: | 15 November 2003 |
| Date Deposited: | 28 Mar 2013 14:26 |
| Last Modified: | 28 Mar 2013 14:26 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/28008 |
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