The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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The antidepressant action of 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid is mediated by phosphorylation of histone deacetylase 5

  • Park, Min Hyeop (Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering) ;
  • Choi, Miyeon (Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University) ;
  • Kim, Yong-Seok (Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering) ;
  • Son, Hyeon (Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering)
  • Received : 2017.08.26
  • Accepted : 2017.12.18
  • Published : 2018.03.01
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Abstract

3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant-like effects in animal models of depression. However, the molecular mechanisms underlying these behavioral actions remain unknown. Here, we demonstrate that CPP rapidly stimulates histone deacetylase (HDAC) 5 phosphorylation and nuclear export in rat hippocampal neurons. These effects are accompanied by calcium/calmodulin kinase II (CaMKII) and protein kinase D (PKD) phosphorylation. Behavioral experiments revealed that viral-mediated hippocampal knockdown of HDAC5 blocked the antidepressant effects of CPP in stressed animals. Taken together, our results imply that CPP acts via HDAC5 and suggest that HDAC5 is a common regulator contributing to the antidepressant actions of NMDA receptor antagonists such as CPP.

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