2. Academic Validation
  3. Phosphodiesterase-2 inhibitor reverses post-traumatic stress induced fear memory deficits and behavioral changes via cAMP/cGMP pathway

Phosphodiesterase-2 inhibitor reverses post-traumatic stress induced fear memory deficits and behavioral changes via cAMP/cGMP pathway

  • Eur J Pharmacol. 2021 Jan 15;891:173768. doi: 10.1016/j.ejphar.2020.173768.
Ling Chen 1,  Kaiping Liu 2,  Yulu Wang 3,  Na Liu 4,  Minjie Yao 5,  Jinlan Hu 6,  Gang Wang 7,  Yindi Sun 8,  Jianchun Pan 9
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, PR China; Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 2 Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 3 College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
  • 4 Department of Traditional Medical Orthopedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shanxi, China.
  • 5 Department of Orthopedics, The People's Hospital of Yichun City, Yichun, Jiangxi Province, China.
  • 6 Department of Anesthesiology, Shanghai Minhang TCM Hospital, Shanghai, China.
  • 7 Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, PR China. Electronic address: wanggang_syyy@163.com.
  • 8 Department of Traditional Medical Orthopedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shanxi, China. Electronic address: xahhsyd@126.com.
  • 9 Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: wenzhoupan2003@yahoo.com.cn.
PMID: 33271150 DOI: 10.1016/j.ejphar.2020.173768
Abstract

Phosphodiesterase 2 is one of the phosphodiesterase (PDEs) family members that regulate cyclic nucleotide (namely cAMP and cGMP) concentrations. The present study determined whether PDE2 inhibition could rescue post-traumatic stress disorder (PTSD)-like symptoms. Mice were subjected to single prolonged stress (SPS) and treated with selective PDE2 Inhibitor Bay 60-7550 (0.3, 1, or 3 mg/kg, i.p.). The behavioral tests such as forced swimming, sucrose preference test, open field, elevated plus maze, and contextual fear paradigm were conducted to determine the effects of Bay 60-7550 on SPS-induced depression- and anxiety-like behavior and fear memory deficits. The results suggested that Bay 60-7550 reversed SPS-induced depression- and anxiety-like behavior and fear memory deficits. Moreover, Bay 60-7550 prevented SPS-induced changes in the adrenal gland index, synaptic proteins synaptophysin and PSD95 expression, PKA, PKG, pCREB, and BDNF levels in the hippocampus and amygdala. These effects were completely prevented by PKG Inhibitor KT5823. While PKA Inhibitor H89 also prevented Bay 60-7550-induced pCREB and BDNF expression, but only partially prevented the effects on PSD95 expression in the hippocampus. These findings suggest that Bay 60-7550 protects mice against PTSD-like stress induced traumatic injury by activation of cGMP- or cAMP-related neuroprotective molecules, such as synaptic proteins, pCREB and BDNF.

Keywords

Fear memory; Phosphodiesterase-2; Post-traumatic stress disorder; Synaptic plasticity; cAMP; cGMP.

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