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Dose-related effects of venlafaxine on pCREB and brain-derived neurotrophic factor (BDNF) in the hippocampus of the rat by chronic unpredictable stress

Published online by Cambridge University Press:  24 June 2014

Jing-Jing Li ,
Yong-Gui Yuan ,
Gang Hou  and
Xiang-Rong Zhang
Jing-Jing Li
Affiliation:
Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China
Yong-Gui Yuan*
Affiliation:
Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China Department of Neuropsychiatry, ZhongDa Hospital, Southeast University, Nanjing, China
Gang Hou
Affiliation:
Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China
Xiang-Rong Zhang
Affiliation:
Department of Neuropsychiatry, ZhongDa Hospital, Southeast University, Nanjing, China
*
Yong-Gui Yuan, Department of Neuropsychiatry, ZhongDa Hospital, Southeast University, DingJiaQiao Road 87#, Nanjing 210009, China. Tel: +86 25 8370 0011/6209; Fax: +86 25 8370 9025; E-mail: yygylh2000@sina.com.cn
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Extract

Background: The molecular pathogenesis of depression and psychopharmacology of antidepressants remain elusive. Recent hypotheses suggest that changes in neurogenesis and plasticity may underlie the aetiology of depression. The hippocampus is affected by depression and shows neuronal remodelling during adulthood.

Objective: The present study on the adult rat hippocampus, was to evaluate the dose-related effects of chronic venlafaxine on the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cyclic-AMP response element binding protein (pCREB).

Methods: Sprague-Dawley rats were exposed to a variety of chronic unpredictable stressors (CUSs) to establish a depression model. Rats were treated for either 14 or 28 days with venlafaxine (5 and 10 mg/kg, respectively). The hippocampal expression of pCREB and BDNF mRNA and protein was assessed by using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction (RT-PCR).

Results: Rats subjected to CUS procedure consumed less sucrose solution compared with non-stressed rats. The CUS influenced exploratory activity resulting in a reduction of the motility counts. Chronic low dose (5 mg/kg, 14 and 28 days), but not high dose (10 mg/kg, 14 and 28 days) of venlafaxine treatment increased the expression of pCREB and BDNF mRNA and protein in the CUS rat hippocampus.

Conclusion: Neuronal plasticity-associated proteins such as pCREB and BDNF play an important role both in stress-related depression and in antidepressant effect.

Keywords

brain-derived neurotrophic factorchronic unpredictable stresscyclic-AMP response element binding proteinhippocampusneurogenesis
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 23 , Issue 1 , February 2011 , pp. 20 - 30
Copyright
Copyright © Cambridge University Press 2011

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