High doses of the histone deacetylase inhibitor sodium butyrate trigger a stress-like response
Abstract
The hypothalamic-pituitary-adrenal (HPA) axis is activated by a wide range of stimuli, including drugs. Here we report that in male rats, a dose of sodium butyrate (NaBu) that is typically used to inhibit histone deacetylation (1200 mg/kg) increased the peripheral levels of HPA hormones and glucose. In a further experiment, we compared the effects of two different doses of NaBu (200 and 1200 mg/kg) and equimolar saline solutions on peripheral neuroendocrine markers and brain c-Fos expression to demonstrate a specific stress-like effect of NaBu that is not related to hypertonicity and to localise putatively involved brain areas. Only the high dose of NaBu increased the plasma levels of stress markers. The equimolar (hypertonic) saline solution also activated the HPA axis and the c-Fos expression in the paraventricular nucleus of the hypothalamus (PVN), a key area for the control of the HPA axis, but the effects were of a lower magnitude than those of NaBu. Regarding other brain areas, group differences in c-Fos expression were not observed in the medial prefrontal cortex or the medial amygdala, but they were observed in the central amygdala and the lateral ventral septum. However, only the latter area of the NaBu group showed enhanced c-Fos expression that was significantly higher than that after hypertonic saline. The present data indicate that high doses of NaBu appear to act as a pharmacological stressor, and this fact should be taken into account when using this drug to st…
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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 Gagliano et al., 2014
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- Authors
- Gagliano, H., Delgado-Morales, R., Sanz-Garcia, A., & Armario, A.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Corresponding author
- Armario, Antonio
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 79
- Pages
- 75-82
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W1977690882
- Cited by
- 76
- References
- 4
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 11 · 2021: 7 · 2020: 4 · 2019: 7 · 2018: 5 · 2017: 1 · 2016: 7 · 2015: 3 · 2014: 2
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministerio de Economía y Competitividad (SAF2011-28313)
- Instituto de Salud Carlos III (RD12/0001/0015)
- Generalitat de Catalunya (SGR2009-16)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Keywords
- sodium butyrate, histone deacetylase inhibitors, hypothalamic-pituitary-adrenal axis, stress response, Fos expression, paraventricular nucleus, central amygdala, medial amygdala, medial prefrontal cortex, plasma glucocorticoids, glucose, hypertonic saline, epigenetics
- MeSH terms
- Acetylation, Adrenocorticotropic Hormone, Animals, Blood Glucose, Brain, Corticosterone, Dose-Response Relationship, Drug, Hippocampus, Histones, Hypothalamus, Male, Mice, Inbred A, Sodium, Stress, Physiological, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Butyric Acid, Rats, Histone Deacetylase Inhibitors
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