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

• Published in: Neurobiology of disease 2008-08, Vol.31 (2), p.278-285
• Main Authors: Qi, Xiaoli, Lin, Wenjuan, Li, Junfa, Li, Huanhuan, Wang, Weiwen, Wang, Donglin, Sun, Meng
• Format: Article
• Language: English
• Subjects: Animals; Antidepressant; Brain - drug effects; Brain - enzymology; Chronic Disease; CREB; 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; ERK; Extracellular Signal-Regulated MAP Kinases - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; Fluoxetine - pharmacology; Hippocampus; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Neurology; Phosphorylation - drug effects; Prefrontal cortex; Rats; Rats, Sprague-Dawley; Serotonin Uptake Inhibitors - pharmacology; Stress; Stress, Psychological - drug therapy; Stress, Psychological - enzymology; Stress, Psychological - physiopathology; Swimming - psychology; Up-Regulation - drug effects; Up-Regulation - physiology
• ISSN: 0969-9961; 1095-953X
• 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.