PMID- 16945350 OWN - NLM STAT- MEDLINE DCOM- 20070801 LR - 20221207 IS - 0006-3223 (Print) IS - 0006-3223 (Linking) VI - 62 IP - 1 DP - 2007 Jul 1 TI - Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse. PG - 55-64 AB - 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. FAU - Schroeder, Frederick A AU - Schroeder FA AD - Brudnick Neuropsychiatric Research Institute, Worcester, Massachusetts, USA. FAU - Lin, Cong Lily AU - Lin CL FAU - Crusio, Wim E AU - Crusio WE FAU - Akbarian, Schahram AU - Akbarian S LA - eng GR - MH074114/MH/NIMH NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060830 PL - United States TA - Biol Psychiatry JT - Biological psychiatry JID - 0213264 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Butyrates) RN - 0 (Enzyme Inhibitors) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Serotonin Uptake Inhibitors) RN - 01K63SUP8D (Fluoxetine) SB - IM CIN - Biol Psychiatry. 2007 Jul 1;62(1):1-3. PMID: 17572174 MH - Animals MH - Antidepressive Agents/*pharmacology MH - Anxiety/psychology MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/metabolism MH - Butyrates/*pharmacology MH - Chromatin Assembly and Disassembly/drug effects MH - Disease Models, Animal MH - Enzyme Inhibitors/*pharmacology MH - Female MH - Fluoxetine/pharmacology MH - Frontal Lobe/drug effects/metabolism MH - Hippocampus/drug effects/metabolism MH - *Histone Deacetylase Inhibitors MH - Immobility Response, Tonic/drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Selective Serotonin Reuptake Inhibitors/pharmacology EDAT- 2006/09/02 09:00 MHDA- 2007/08/02 09:00 CRDT- 2006/09/02 09:00 PHST- 2006/03/27 00:00 [received] PHST- 2006/05/26 00:00 [revised] PHST- 2006/06/28 00:00 [accepted] PHST- 2006/09/02 09:00 [pubmed] PHST- 2007/08/02 09:00 [medline] PHST- 2006/09/02 09:00 [entrez] AID - S0006-3223(06)00861-4 [pii] AID - 10.1016/j.biopsych.2006.06.036 [doi] PST - ppublish SO - Biol Psychiatry. 2007 Jul 1;62(1):55-64. doi: 10.1016/j.biopsych.2006.06.036. Epub 2006 Aug 30.