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Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment
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Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core symptom of depression, was assessed by measuring consumption of a palatable solution. Exposure to CUS reduced intake of a palatable solution and this effect was prevented by chronic antidepressant treatment. Moreover, chronic antidepressant treatment decreased depressive-like behavior in a modified forced swim test in stressed rats. Present evidence suggests a role for brain-derived neurotrophic factor (BDNF) in depression. BDNF mRNA levels in the ventral and dorsal hippocampus were assessed by in situ hybridization. Exposure to CUS was not correlated with a decrease but rather with an increase in BDNF mRNA expression in both the dentate gyrus of the dorsal hippocampus and the CA3 region of the ventral hippocampus indicating that there is no simple link between depression-like behaviors per se and brain BDNF levels in rats. However, a significant increase in BDNF mRNA levels in the dentate gyrus of the dorsal hippocampus correlated with chronic antidepressant treatment emphasizing a role for BDNF in the mechanisms underlying antidepressant activity.
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“Both MDD patients [57–59] and animal models of depression [60, 61] show a remarkable reduction in serum BDNF levels.”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [61]
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Metadata
- Authors
- Larsen, M. H., Mikkelsen, J. D., Hay-Schmidt, A., & Sandi, C.
- Affiliations
- University of Copenhagen (DK)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Larsen, Marianne H.
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 44
- Issue
- 13
- Pages
- 808-816
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2078116925
- Cited by
- 165
- References
- 71
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 14 · 2020: 7 · 2019: 10 · 2018: 11 · 2017: 5 · 2016: 6 · 2015: 17 · 2014: 15 · 2013: 10 · 2012: 16
- FWCI
- 12.67
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (FP7-HEALTH-F2M-2007-201600, 120791)
- FP7 Health
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- brain-derived neurotrophic factor, chronic unpredictable mild stress, depression, anhedonia, antidepressant treatment, venlafaxine, imipramine, hippocampus, dentate gyrus, CA3 region, BDNF mRNA expression, forced swim test
- MeSH terms
- Venlafaxine Hydrochloride, Animals, Antidepressive Agents, Cyclohexanols, Disease Models, Animal, Food Preferences, Hippocampus, Imipramine, Locomotion, Male, RNA, Messenger, Saccharin, Stress, Psychological, Sweetening Agents, Swimming, Time Factors, Rats, Sprague-Dawley, In Situ Hybridization, Maze Learning, Dentate Gyrus, Brain-Derived Neurotrophic Factor, Rats, CA3 Region, Hippocampal
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