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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

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 demonstr...

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Detalles Bibliográficos
Autores principales: Park, Min Hyeop, Choi, Miyeon, Kim, Yong-Seok, Son, Hyeon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Physiological Society and The Korean Society of Pharmacology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840074/
https://www.ncbi.nlm.nih.gov/pubmed/29520168
http://dx.doi.org/10.4196/kjpp.2018.22.2.155
Descripción
Sumario: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.