Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression
Abstract
Rationale Brain-derived neurotrophic factor (BDNF) and signaling at its receptor, tropomyosin-related kinase B (TrkB), are implicated in the rapid and long-lasting antidepressant effects of ketamine. Moreover, a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), and/or TrkB antagonist, ANA-12, shows antidepressant effects in animal models of depression. Objective The objective of this study is to compare the influence of ketamine, 7,8-DHF, and ANA-12 on antidepressant activity in the social defeat stress model. Results In the tail suspension and forced swimming tests, ketamine, 7,8-DHF, or ANA-12 markedly attenuated the increased immobility time in depressed mice compared with the vehicle-treated group. In the sucrose preference test, all drugs significantly improved the reduced preference in depressed mice at both 1 and 3 days after a single dose. Antidepressant effect of ketamine, but not 7,8-DHF or ANA-12, was still detectable 7 days after a single dose. Western blot analyses showed that ketamine, but not 7,8-DHF or ANA-12, markedly attenuated reduced levels of BDNF and postsynaptic density protein 95 (PSD-95) in the prefrontal cortex (PFC), dentate gyrus (DG), and CA3 of the hippocampus in depressed mice 8 days after a single dose. Furthermore, ketamine markedly increased reduced levels of GluA1 in the PFC and DG of depressed mice. In contrast, ketamine showed no effect against increased levels of BDNF, PSD-95, and GluA1 observed in the nucleus accumbens of depressed mice. Con…
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In a rat model of depression, increases in BDNF in the VTA-NAc induce pro-depressive-like effects.
“Knowing that, in a rat model of depression, increases in BDNF in the VTA-NAc (Shirayama et al. 2015; Zhang et al. 2015b) induced pro-depressive-like effects (Eisch et al. 2003)”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Zhang et al. 2015b
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- Authors
- Zhang, J.-C., Yao, W., Dong, C., Yang, C., Ren, Q., Ma, M., Han, M., & Hashimoto, K.
- Affiliations
- Chiba University (JP)
- Corresponding author
- Hashimoto, Kenji
- Venue
- Psychopharmacology
- Published
- 2015-09-04
- Volume
- 232
- Issue
- 23
- Pages
- 4325-4335
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W1248807947
- Cited by
- 183
- References
- 10
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 13 · 2023: 7 · 2022: 14 · 2021: 17 · 2020: 20 · 2019: 29 · 2018: 20 · 2017: 17 · 2016: 26 · 2015: 2
- FWCI
- 15.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Daiichi-Sankyo
- Japan Society for the Promotion of Science (15K19711, 24116006)
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- ketamine, 7,8-dihydroxyflavone, ANA-12, antidepressant effects, social defeat stress, depression, brain-derived neurotrophic factor, TrkB receptor, synaptogenesis, PSD-95, GluR1, prefrontal cortex, hippocampus, nucleus accumbens
- MeSH terms
- Animals, Antidepressive Agents, Azepines, Benzamides, Depression, Disease Models, Animal, Hippocampus, Ketamine, Male, Mice, Inbred C57BL, Nucleus Accumbens, Stress, Psychological, Swimming, Prefrontal Cortex, Brain-Derived Neurotrophic Factor, Hindlimb Suspension, Flavones, Mice
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