Antidepressant action of HDAC inhibition in the prefrontal cortex
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Previous research has demonstrated antidepressant-like effects in rodents upon intracerebral inhibition of histone deacetylases (HDACs). Such effects have been reported for local HDAC inhibition in the nucleus accumbens, hippocampus, and amygdala. However, the effect of HDAC inhibition within the medial prefrontal cortex, which is integral to depression-related symptoms and their treatment, remains unknown. Here we show that local infusion of the highly selective HDAC inhibitor, MS-275, into the medial prefrontal cortex exerts robust antidepressant-like effects in the chronic social defeat stress paradigm in mice. These findings provide further impetus for the assessment of HDAC inhibitors for the treatment of depression.
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In chronic social defeat stress models, entinostat produces antidepressant-like effects.
“In chronic social defeat stress models, entinostat produces antidepressant-like effects (Dai et al., 2021; Covington et al., 2015), reinforcing the link between deacetylation-targeted interventions and stress-related phenotypes.”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Covington et al., 2015
The Results (§3.2; page unavailable) report antidepressant-like effects after MS-275 infusion into the prefrontal cortex of mice subjected to chronic social defeat stress. Our copy does not identify MS-275 as entinostat, so it does not establish the claim for the named drug. (LLM, conf=0.79)
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- Authors
- Covington, H. E., Maze, I., Vialou, V., & Nestler, E. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 298
- Pages
- 329-335
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC4441835
- OpenAlex
- W1971255987
- Cited by
- 97
- References
- 31
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 10 · 2023: 5 · 2022: 8 · 2021: 8 · 2020: 6 · 2019: 10 · 2018: 7 · 2017: 15 · 2016: 8 · 2015: 2
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health
- Depression Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- histone deacetylase inhibition, histone deacetylase inhibitors, entinostat, antidepressant effects, medial prefrontal cortex, chronic social defeat stress, depression, intracerebral infusion, local drug delivery
- MeSH terms
- Histone Deacetylase 3, Analysis of Variance, Animals, Antineoplastic Agents, Benzamides, Disease Models, Animal, Fluoxetine, Histone Deacetylases, Male, Mice, Inbred C57BL, Pyridines, Stress, Psychological, Prefrontal Cortex, Antidepressive Agents, Second-Generation, Mice, Hypodermoclysis
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