Antidepressant action of HDAC inhibition in the prefrontal cortex

Neuroscience. 2015 Jul 9;298:329-35. doi: 10.1016/j.neuroscience.2015.04.030. Epub 2015 Apr 20.


Previous research has demonstrated antidepressant-like effects in rodents upon intracerebral inhibition of histone deacetylases (HDACs). Such effects have been reported for local HDAC inhibition in the nucleus accumbens, hippocampus, and amygdala. However, the effect of HDAC inhibition within the medial prefrontal cortex, which is integral to depression-related symptoms and their treatment, remains unknown. Here we show that local infusion of the highly selective HDAC inhibitor, MS-275, into the medial prefrontal cortex exerts robust antidepressant-like effects in the chronic social defeat stress paradigm in mice. These findings provide further impetus for the assessment of HDAC inhibitors for the treatment of depression.

Keywords: HDAC inhibitors; MS-275; depression; gene expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antidepressive Agents, Second-Generation / administration & dosage*
  • Antineoplastic Agents / pharmacology*
  • Benzamides / pharmacology
  • Disease Models, Animal
  • Fluoxetine / administration & dosage
  • Histone Deacetylases / metabolism*
  • Hypodermoclysis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / enzymology*
  • Pyridines / pharmacology
  • Stress, Psychological / drug therapy
  • Stress, Psychological / pathology*


  • Antidepressive Agents, Second-Generation
  • Antineoplastic Agents
  • Benzamides
  • Pyridines
  • Fluoxetine
  • entinostat
  • Histone Deacetylases
  • histone deacetylase 3