1. Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation.
- Author
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Alme MN, Wibrand K, Dagestad G, and Bramham CR
- Subjects
- ADP-Ribosylation Factors genetics, Animals, Brain anatomy & histology, Brain metabolism, Brain-Derived Neurotrophic Factor pharmacology, C-Reactive Protein genetics, Carrier Proteins, DNA-Binding Proteins genetics, Depressive Disorder drug therapy, Depressive Disorder metabolism, Depressive Disorder physiopathology, Drug Administration Schedule, Drug Resistance genetics, GPI-Linked Proteins, Long-Term Potentiation genetics, Male, Neuropeptides genetics, Phosphoproteins genetics, Rats, Selective Serotonin Reuptake Inhibitors pharmacology, Stress, Psychological complications, Stress, Psychological metabolism, Stress, Psychological physiopathology, Time Factors, Transcription Factors genetics, Up-Regulation drug effects, Up-Regulation genetics, Brain drug effects, Brain-Derived Neurotrophic Factor metabolism, Fluoxetine pharmacology, Gene Expression Regulation drug effects, Long-Term Potentiation drug effects, Nerve Tissue Proteins genetics
- Abstract
Several lines of evidence implicate BDNF in the pathogenesis of stress-induced depression and the delayed efficacy of antidepressant drugs. Antidepressant-induced upregulation of BDNF signaling is thought to promote adaptive neuronal plasticity through effects on gene expression, but the effector genes downstream of BDNF has not been identified. Local infusion of BDNF into the dentate gyrus induces a long-term potentiation (BDNF-LTP) of synaptic transmission that requires upregulation of the immediate early gene Arc. Recently, we identified five genes (neuritin, Narp, TIEG1, Carp, and Arl4d) that are coupregulated with Arc during BDNF-LTP. Here, we examined the expression of these genes in the dentate gyrus, hippocampus proper, and prefrontal cortex after antidepressant treatment. We show that chronic, but not acute, fluoxetine administration leads to upregulation of these BDNF-LTP-associated genes in a brain region-specific pattern. These findings link chronic effects of antidepressant treatment to molecular mechanisms underlying BDNF-induced synaptic plasticity.
- Published
- 2007
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