title: cAMP/PKA/CREB/GLT1 signaling involved in the antidepressant-like effects of phosphodiesterase 4D inhibitor (GEBR-7b) in rats.
abstract: OBJECTIVE
  GEBR-7b, a potential phosphodiesterase 4D inhibitor, has been shown to have memory-enhancing effects in rodents. However, it is still unknown whether GEBR-7b also has the antidepressant-like effects in rats. Herein, we examined the potential of GEBR-7b to attenuate depression-like behaviors in the rat model of depression induced by chronic unpredictable stress (CUS). Next, we also investigated the alterations of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) catalytic subunit (PKAca), cAMP response element-binding (CREB), and glutamate transporter 1 (GLT1) levels produced by GEBR-7b in the rats model of depression.
  
  
  METHODS
  Effects of GEBR-7b on CUS (35 days)-induced depression-like behaviors were examined by measuring immobility time in the forced swimming test (FST). Hippocampal cAMP levels were examined by enzyme-linked immunosorbent assay, whereas PKAca, phosphorylation of CREB (pCREB), CREB, and GLT1 in the hippocampus of rats were subjected to Western blot analysis.
  
  
  RESULTS
  CUS exposure caused a depression-like behavior evidenced by the increased immobility time in FST. Depression-like behavior induced by CUS was accompanied by a significant increased GLT, decreased cAMP, PKAca, pCREB activities in hippocampus. However, repeated GEBR-7b administration significantly reversed CUS-induced depression-like behavior and changes of cAMP/PKA/CREB/GLT1 signaling. No alteration was observed in locomotor activity in open field test.
  
  
  CONCLUSIONS
  These findings indicate that GEBR-7b reversed the depression-like behaviors induced by CUS in rats, which is at least in part mediated by modulating cAMP, PKAca, pCREB, and GLT1 levels in the hippocampus of rats, supporting its neuroprotective potential against behavioral and biochemical dysfunctions induced by CUS.
authors: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China; Department of Pharmacy, General Hospital of Chinese People's Armed Police Forces, Beijing, Zhejiang, People's Republic of China.
authors: Xu
authors: X
authors: Liu
authors: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors: Haibiao
authors: H
authors: Guo
authors: Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University, Ningbo, Zhejiang, People's Republic of China; Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, People's Republic of China.
authors: Mohammad Daud Som
authors: MD
authors: Sayed
authors: Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University, Ningbo, Zhejiang, People's Republic of China; Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, People's Republic of China.
authors: Yang
authors: Y
authors: Lu
authors: Department of Pediatrics, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People's Republic of China.
authors: Ting
authors: T
authors: Yang
authors: Department of Geriatric Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, People's Republic of China.
authors: Dongsheng
authors: D
authors: Zhou
authors: Department of Geriatric Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, People's Republic of China.
authors: Zhongming
authors: Z
authors: Chen
authors: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors: Haitao
authors: H
authors: Wang
authors: Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University, Ningbo, Zhejiang, People's Republic of China; Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, People's Republic of China.
authors: Chuang
authors: C
authors: Wang
authors: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors: Jiangping
authors: J
authors: Xu
keywords: GEBR-7b; cAMP response element-binding protein; cyclic adenosine monophosphate; glutamate transporter 1; phosphodiesterase 4D; phosphorylation of CREB; protein kinase Aca