Original ArticleAntidepressant-Like Effects of the Histone Deacetylase Inhibitor, Sodium Butyrate, in the Mouse
Section snippets
Animals
All experiments were conducted with adult male and female C57BL/6J inbred mice (age 9–22 weeks). Animals were housed in groups of 2–4/cage with food and water ad libitum. Animals were purchased directly from the Jackson Laboratory (Bar Harbor, Maine), housed under 12-hour light/dark cycle, and allowed to acclimate to new housing for at least 5–7 days before experimental manipulation. All experimental procedures were approved by the Institutional Animal Care and Use Committee of the University
Systemic Administration of Sodium Butyrate Induces a Transient Increase in Histone Acetylation in Brain and Liver
Butyrate inhibits the activity of most HDAC forms, except class II HDAC 6 and HDAC10 and all class III HDACs (Davie 2003). Previous studies showed that peripheral administration of SB upregulates overall levels of histone acetylation in brain chromatin, but dose-response and temporal course of this effect remain unclear (Dong et al 2005, Ferrante et al 2003). Therefore, we injected mice with 1.2 g/kg SB, a dose that ameliorates the neurological phenotype in a mouse model for Huntington’s
Discussion
We report that in mice, the HDACi SB improves performance in a behavioral despair paradigm, the TST. Notably, combined treatment with SB and the SSRI fluoxetine was superior to fluoxetine monotherapy both in the acute and chronic paradigm. In addition, mice that received SB as a single drug via daily injections over a period of 3 weeks showed a significant improvement in the TST, when applied within a battery of four tests designed to measure behavioral correlates of anxiety and despair. In
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