Cited by 112Treatment of Major DepressionHistone Deacetylase Inhibitors ResearchNeurotransmitter Receptor Influence on Behavior

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Effects of the histone deacetylase inhibitor sodium butyrate in models of depression and anxiety

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Gundersen, Brigitta B., Blendy, Julie A.·2009·Neuropharmacology

DOI 10.1016/j.neuropharm.2009.04.008PMC PMC2702471

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Abstract

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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Authors: Gundersen, B. B., & Blendy, J. A.
Affiliations: University of Pennsylvania (US)
Corresponding author: Blendy, Julie A.
ORCID: Gundersen, Brigitta B.
Blendy, Julie A.
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2009-07
Volume: 57
Issue: 1
Pages: 67-74
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/j.neuropharm.2009.04.008
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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 (medical) › 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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Effects of the histone deacetylase inhibitor sodium butyrate in models of depression and anxiety

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