Research Papers:

Beneficial effect of fluoxetine treatment aganist psychological stress is mediated by increasing BDNF expression in selected brain areas

Gongying Li, Ping Jing, Zhidong Liu, Zhiruo Li, Hongxia Ma, Wenzhen Tu, Wei Zhang and Chuanjun Zhuo _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:69527-69537. https://doi.org/10.18632/oncotarget.17891

Metrics: PDF 1440 views  |   HTML 2782 views  |   ?  


Gongying Li1,*, Ping Jing2,*, Zhidong Liu3,*, Zhiruo Li4, Hongxia Ma5, Wenzhen Tu2,#, Wei Zhang2,# and Chuanjun Zhuo2,1,6,7,#

1 Insitute of Mental health, Jining Medical University, Jining, 272067, China

2Department of Psychiatry, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang Province, 325000, China

3Tianjin Fourth Central Hospital of Tianjin Medical University, Tianjin, 300000, China

4Department of Neurology, The Affiliated Hospital of Jining Medical University, Jining, 272000, China

5Department of Psychiatry, The Second Affiliated Hospital of Jining Medical University, Jining, 272051, China

6Department of Psychiatric Neuroimaging Laboratory, Tianjin Anding Hospital, Tianjin Mental Health Center, Tianjin 300222, China

7Department of Psychiatry, Tianjin Anning Hospital, Tianjin 300300, China

*These authors have contributed equally to this work

#Co First authors

Correspondence to:

Chuanjun Zhuo, email: [email protected]

Keywords: brain-derived neurotrophic factor (BDNF), psychological stress, fluoxetine, serotonin

Received: January 23, 2017     Accepted: April 29, 2017     Published: May 15, 2017


SSRI antidepressant fluoxetine is widely used to treat psychological stress related disorders, however the underlying working mechanisms is not fully understood, as SSRIs can rapidly increase the extracellular serotonin levels but it normally takes weeks to reveal their therapeutic effect in the stress-related psychological disorders. Our previous study demonstrated that purely psychological stress without any physic stimuli induces a biphasic change in the expression of brain-derived neurotrophic factor (BDNF), which immediately decrease and then gradually increase after the stress; and that the latter BDNF increase in response to the psychological stress involves the activation of serotonin system. To investigate the role of BDNF in the fluoxetine treatment for stress-related psychological disorders, we examined the mRNA and protein levels of BDNF in the brain of Sprague-Dawley (SD) rats, which were pretreated with fluoxetine at 10 mg/kg or vehicle solution for 14 days, over 24 hour after an acute psychological stress exposure. In situ hybridization and immunohistochemistry were performed to detect the expression of BDNF at different time points in various brain regions after the psychological stress. We found that fluoxetine treatment completely blocked the BDNF decrease induced by the psychological stress, and also enhanced the gradual increase in the expression of BDNF in most of the brain regions except VTA after the psychological stress. The results suggest that the enhancement in BDNF levels induced by chronic fluoxetine treatment mediates the therapeutic effect against psychological stress.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 17891