Dopamine D2‐like antagonists induce chromatin remodeling in striatal neurons through cyclic AMP‐protein kinase A and NMDA receptor signaling

• DOI: 10.1111/j.1471-4159.2004.02569.x
• Publication Date: 2004-08-16T14:44:00Z
• Authors: Jianhong Li; Yin Guo; Frederick A. Schr...; Rachael M. Youngs; Thomas W. Schmidt; Craig Ferris; Christine Konradi; Schahram Akbarian
• Keywords: Adenosine A2A receptor

Abstract Antipsychotic drugs regulate gene transcription in striatal neurons by blocking dopamine D 2 ‐like receptors. Little is known about the underlying changes chromatin structure, including covalent modifications at histone N‐terminal tails that are epigenetic regulators of expression. We show treatment with antagonists rapidly induces phosphorylation H3 serine 10 and acetylation H3‐lysine 14 bulk from striatum nuclei neurons. find that, vivo , antagonist‐induced phospho‐acetylation inhibited NMDA receptor antagonist MK‐801 protein kinase A (PKA) inhibitor Rp‐adenosine 3c′,5c′‐cyclic monophosphorothioate triethylammonium salt but increased PKA activator Sp‐adenosine salt. Furthermore, dissociated cultures which lack midbrain cortical pre‐synaptic inputs, was induced glutamate, l ‐type Ca 2+ channel agonists activators cAMP‐dependent or antagonists. The dual modification, H3pS10‐acK14, enriched genomic sites active showed kinetics early response. Together, these results suggest structure dynamically regulated dopaminergic glutamatergic inputs converging on cellular level. Blockade receptors phospho‐acetylation, through PKA, post‐synaptic signaling.