title: Chronic Fluoxetine Treatment Upregulates the Activity of the ERK1/2-NF-κB Signaling Pathway in the Hippocampus and Prefrontal Cortex of Rats Exposed to Forced-Swimming Stress.
abstract: OBJECTIVE
  The aim of this study was to explore whether or not the antidepressant actions of fluoxetine (FLX) are correlated with extracellular signal-regulated kinase 1 and 2 (ERK1/2) and nuclear factor κ-light chain enhancer of activated B cells (NF-κB) in the hippocampus (HC) and prefrontal cortex (PFC) of rats.
  
  
  METHODS
  A total of 108 male Sprague-Dawley rats were randomly divided into 6 groups of 18 rats each. Group 1 was the control group, while group 2 comprised the depressed model in which rats were subjected to 28 days of forced-swimming stress (FST); groups 3-6 were also subjected to 28 days of FST and treated with FLX once a day for 1 day (group 3; F1d), 1 week (group 4; F1w), 2 weeks (group 5; F2w), or 4 weeks (group 6; F4w). The control group was not subjected to FST or treated with FLX. Behavior tests that included the Morris water maze (MWM) and saccharin preference were performed, and ERK1/2 and NF-κB proteins were assayed using Western blot.
  
  
  RESULTS
  The rats in the control group and in groups 5 and 6 (F2w and F4w, respectively) had a significantly shorter average escape latency, needed more attempts in order to successfully cross the platform, and had a greater saccharin preference than those in the depressed group (p < 0.05). In the depressed group, the phosphorylated ERK1/2 (p-ERK1/2) and phosphorylated NF-κB (p-NF-κB) expression in the HC and PFC were lower than in the control group (p < 0.05). Treatment with FLX reversed the changes in the expression of p-ERK1/2 and p-NF-κB in rats in the F2w and F4w groups.
  
  
  CONCLUSIONS
  In this study, FLX treatment for 2 weeks or longer reversed the impaired spatial learning, memory, and anhedonia observed in the depressed model rats and upregulated the activities of the ERK1/2-NF-κB signaling pathway.
authors.affiliation: Department of Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Jingqiu
authors.initials: J
authors.lastname: Cui
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.forename: Xue
authors.initials: X
authors.lastname: Yu
authors.forename: Jing-Lan
authors.initials: JL
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hengfen
authors.initials: H
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D003865:Major Depressive Disorder / Q000188:drug therapy*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D007858:Learning / Q000187:drug effects; D020935:MAP Kinase Signaling System; D008297:Male; D016328:NF-kappa B / Q000187:drug effects*; D017397:Prefrontal Cortex; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological; D013550:Swimming / Q000523:psychology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D016328:NF-kappa B; D005473:Fluoxetine; D048049:Extracellular Signal-Regulated MAP Kinases