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Cited by 113Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorStress Responses and Cortisol

Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression

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Haenisch, Britta, Bilkei‐Gorzo, Andras, Caron, Marc G., Bönisch, Heinz·2009·Journal of Neurochemistry
DOI 10.1111/j.1471-4159.2009.06345.xPMC PMC2764285
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Abstract

Diverse factors such as changes in neurotrophins and brain plasticity have been proposed to be involved in the actions of antidepressant drugs (ADs). However, in mouse models of depression based on chronic stress, it is still unclear whether simultaneous changes in behavior and neurotrophin expression occur and whether these changes can be corrected or prevented comparably by chronic administration of ADs or genetic manipulations that produce antidepressant‐like effects such as the knockout of the norepinephrine transporter (NET) gene. Here we show that chronic restraint or social defeat stress induce comparable effects on behavior and changes in the expression of neurotrophins in depression‐related brain regions. Chronic stress caused down‐regulation of BDNF, nerve growth factor, and neurotrophin‐3 in hippocampus and cerebral cortex and up‐regulation of these targets in striatal regions. In wild‐type mice, these effects could be prevented by concomitant chronic administration of five pharmacologically diverse ADs. In contrast, NET knock out (NETKO) mice were resistant to stress‐induced depressive‐like changes in behavior and brain neurotrophin expression. Thus, the resistance of the NETKO mice to the stress‐induced depression‐associated behaviors and biochemical changes highlight the importance of noradrenergic pathways in the maintenance of mood. In addition, these mice represent a useful model to study depression‐resistant behaviors, and they might help to provide deeper insights into the identification of downstream targets involved in the mechanisms of antidepressants.

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  • Genetically modified mice strains bred on C57BL/6J background are extremely useful in understanding the genetic basis of depression-like behavioral traits.

    “Genetically modified mice strains bred on C57BL/6J background are extremely useful in understanding the genetic basis of depression-like behavioral traits26,42,43.”

    From A standardized protocol for repeated social defeat stress in mice (2011) · cites this paper as [43]

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Cited by

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Authors
Haenisch, B., Bilkei‐Gorzo, A., Caron, M. G., & Bönisch, H.
Affiliations
  • University of Bonn (DE)
  • Duke University (US)
Corresponding author
Bönisch, Heinz
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2009-09-23
Volume
111
Issue
2
Pages
403-416
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/j.1471-4159.2009.06345.x
PMC
PMC2764285
OpenAlex
W2019771665
Cited by
113
References
5
Citations by year
2026: 2 · 2025: 4 · 2024: 5 · 2023: 1 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 7 · 2017: 7 · 2016: 11 · 2015: 5 · 2014: 11 · 2013: 7 · 2012: 6
FWCI
7.09
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Studienstiftung des Deutschen Volkes
  • National Institutes of Health
  • National Institute of Mental Health (P50MH060451)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
norepinephrine transporter, antidepressants, chronic stress, depression, neurotrophins, brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, restraint stress, social defeat stress, noradrenergic pathways, hippocampus, cerebral cortex, striatum
MeSH terms
Animals, Antidepressive Agents, Behavior, Animal, Brain Stem, Cerebellum, Chronic Disease, Depressive Disorder, Disease Models, Animal, Female, Male, Mice, Inbred C57BL, Nerve Growth Factors, Olfactory Bulb, Restraint, Physical, RNA, Messenger, Social Behavior, Stress, Psychological, Swimming, Mice, Knockout, Brain-Derived Neurotrophic Factor, Nerve Growth Factor, Norepinephrine Plasma Membrane Transport Proteins, Mice

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