Effects of the histone deacetylase inhibitor sodium butyrate in models of depression and anxiety
Open accessAbstract
Histone modification, which affects the rate of transcription without altering DNA sequence, occurs in response to various psychiatric drugs and in several models of psychiatric disease. As increases in histone acetylation have been seen after treatment with antidepressants, we investigated whether directly increasing histone acetylation using a histone deacetylase inhibitor would have antidepressant effects. We administered sodium butyrate (NaB, 100 mg/kg, i.p.) to mice acutely (3 injections over 24 h) or chronically (twice daily for 21 days) and subjected them to a number of behavioral tests of antidepressant response. This dose of NaB had no effect on overall locomotor activity after either acute or chronic treatment. Acutely treated mice showed an increase in immobility in the forced-swim test (FST) and an increase in latency to consume in the novel environment of the novelty-induced hypophagia (NIH) paradigm, an anxiogenic effect. The effect of NaB on anxiety did not generalize to another test, the elevated zero maze, where it had no effect. Chronic treatment with NaB had no effect on latency to consume in the NIH or immobility in the FST. However, this dose did alter histone acetylation in the hippocampus. While H4 acetylation increased in the hippocampus 30 min following acute NaB, chronic treatment caused a decrease in AcH4. There were no changes in AcH3 following either treatment. While changes in chromatin structure may be involved in the mechanism of action of antidepressant drugs, these data suggest that increasing histone acetylation pharmacologically is not sufficient to produce antidepressant effects.
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Using this method of administration results in a stress-like effect and increased anxiety-like behavior.
“using this method of administration results in a stress-like effect and increased anxiety-like behavior”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Gundersen and Blendy, 2009
The Results (§3.2; page unavailable) report increased anxiety-like behavior after acute sodium butyrate injections in mice, and the Discussion (§4; page unavailable) calls this an anxiogenic effect. The paper does not report a stress-like effect or establish that the method of administration itself, rather than the drug treatment, caused the behavior. (LLM, conf=0.84)
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The Effects of Long-term Exposure to Bisphenol-A on Fear Memory of Adult Mice
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- Authors
- Gundersen, B. B., & Blendy, J. A.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Blendy, Julie A.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 57
- Issue
- 1
- Pages
- 67-74
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC2702471
- OpenAlex
- W1996116694
- Cited by
- 112
- References
- 32
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 12 · 2019: 7 · 2018: 4 · 2017: 7 · 2016: 9 · 2015: 6 · 2014: 5 · 2013: 12 · 2012: 9
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (U01MH072832)
- National Institute on Drug Abuse (R01DA011649)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- sodium butyrate, histone deacetylase inhibitors, histone acetylation, depression, anxiety, antidepressant effects, forced swim test, novelty-induced hypophagia, elevated zero maze, hippocampus, histone H4 acetylation, histone H3 acetylation, chromatin structure, locomotor activity
- MeSH terms
- Acetylation, Analysis of Variance, Animals, Antidepressive Agents, Tricyclic, Anxiety, Butyrates, Chlordiazepoxide, Depression, Desipramine, Disease Models, Animal, Drug Administration Schedule, Enzyme Inhibitors, Exploratory Behavior, Hippocampus, Histone Deacetylases, Histones, Mice, Inbred C57BL, Motor Activity, Swimming, Time Factors, Anti-Anxiety Agents, Maze Learning, Mice, Histone Deacetylase Inhibitors
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