Fluoxetine increases the activity of the ERK-CREB signal system and alleviates the depressive-like behavior in rats exposed to chronic forced swim stress

Xiaoli Qi; Wenjuan Lin; Junfa Li; Huanhuan Li; Weiwen Wang; Donglin Wang; Meng Sun

doi:10.1016/j.nbd.2008.05.003

Fluoxetine increases the activity of the ERK-CREB signal system and alleviates the depressive-like behavior in rats exposed to chronic forced swim stress

Neurobiol Dis. 2008 Aug;31(2):278-85. doi: 10.1016/j.nbd.2008.05.003. Epub 2008 May 20.

Authors

Xiaoli Qi¹, Wenjuan Lin, Junfa Li, Huanhuan Li, Weiwen Wang, Donglin Wang, Meng Sun

Affiliation

¹ Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Science, Beijing, 100101, China.

PMID: 18586506
DOI: 10.1016/j.nbd.2008.05.003

Abstract

Our previous research indicates that the extracellular signal-regulated kinase (ERK)-cyclic AMP-responsive-element-binding protein (CREB) signal system may be involved in the molecular mechanism of depression. The present study further investigated the effect of antidepressant fluoxetine on the ERK-CREB signal system and the depressive-like behaviors in rats. Fluoxetine was administrated to either naive rats or stressed rats for 21 days. The results showed that chronic forced swim stress induced depressive-like behaviors and decreased the levels of P-ERK2, P-CREB, ERK1/2 and CREB in hippocampus and prefrontal cortex. Fluoxetine alleviated the depressive-like behaviors and reversed the disruptions of the P-ERK2 and P-CREB in stressed rats. Fluoxetine also exerted mood-elevating effect and increased the levels of the P-ERK2 and P-CREB in naive rats. These results suggest that the ERK-CREB signal system may be the targets of the antidepressant action of fluoxetine and participate in the neuronal mechanism of depression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / drug effects*
Brain / enzymology
Chronic Disease
Cyclic AMP Response Element-Binding Protein / drug effects*
Cyclic AMP Response Element-Binding Protein / metabolism
Depressive Disorder / drug therapy*
Depressive Disorder / enzymology
Depressive Disorder / physiopathology
Disease Models, Animal
Down-Regulation / drug effects
Down-Regulation / physiology
Extracellular Signal-Regulated MAP Kinases / drug effects*
Extracellular Signal-Regulated MAP Kinases / metabolism
Fluoxetine / pharmacology*
MAP Kinase Signaling System / drug effects
MAP Kinase Signaling System / physiology
Male
Phosphorylation / drug effects
Rats
Rats, Sprague-Dawley
Selective Serotonin Reuptake Inhibitors / pharmacology
Stress, Psychological / drug therapy*
Stress, Psychological / enzymology
Stress, Psychological / physiopathology
Swimming / psychology
Up-Regulation / drug effects
Up-Regulation / physiology

Substances

Cyclic AMP Response Element-Binding Protein
Serotonin Uptake Inhibitors
Fluoxetine
Extracellular Signal-Regulated MAP Kinases