Antidepressant-Like Effects of the Histone Deacetylase Inhibitor, Sodium Butyrate, in the Mouse
Biological Psychiatry. 2007-07-01; 62(1): 55-64
DOI: 10.1016/j.biopsych.2006.06.036
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1. Biol Psychiatry. 2007 Jul 1;62(1):55-64. Epub 2006 Aug 30.
Antidepressant-like effects of the histone deacetylase inhibitor, sodium
butyrate, in the mouse.
Schroeder FA(1), Lin CL, Crusio WE, Akbarian S.
Author information:
(1)Brudnick Neuropsychiatric Research Institute, Worcester, Massachusetts, USA.
Comment in
Biol Psychiatry. 2007 Jul 1;62(1):1-3.
BACKGROUND: Chromatin remodeling, including changes in histone acetylation, might
play a role in the pathophysiology and treatment of depression. We investigated
whether the histone deacetylase inhibitor sodium butyrate (SB) administered as
single drug or in combination with the selective serotonin reuptake inhibitor
(SSRI) fluoxetine exerts antidepressant-like effects in mice.
METHODS: Mice (C57BL/6J) received injections of SB, fluoxetine, or a combination
of both drugs either acutely or chronically for a period of 28 days and were
subjected to a battery of tests to measure anxiety and behavioral despair.
Histone acetylation and expression of brain-derived neurotrophic factor (BDNF)
were monitored in hippocampus and frontal cortex.
RESULTS: Co-treatment with SB and fluoxetine resulted in a significant 20%-40%
decrease in immobility scores in the tail suspension test (TST), a measure for
behavioral despair, both acutely and chronically. In contrast, decreased
immobility after single drug regimens was limited either to the acute
(fluoxetine) or chronic (SB) paradigm. Systemic injection of SB induced
short-lasting histone hyperacetylation in hippocampus and frontal cortex. Among
the four treatment paradigms that resulted in improved immobility scores in the
TST, three were associated with a transient, at least 50% increase in BDNF
transcript in frontal cortex, whereas changes in hippocampus were less
consistent.
CONCLUSIONS: The histone deacetylase inhibitor SB exerts antidepressant-like
effects in the mouse. The therapeutic benefits and molecular actions of histone
modifying drugs, including co-treatment with SSRIs and other newer generation
antidepressant medications, warrant further exploration in experimental models.
DOI: 10.1016/j.biopsych.2006.06.036
PMID: 16945350 [Indexed for MEDLINE]