HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity.

The authors show that chronic treatment with antipsychotic drugs decreases expression of mGlu2 and histone acetylation at its promoter in frontal cortex. This is mediated through 5-HT2A receptor–dependent upregulation of HDAC2. HDAC inhibitors prevent this decrease in mGluR2, augmenting the behavioral effects of antipsychotics.