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Growing evidence supports the involvement of brain-derived neurotrophic factor (BDNF) in mood disorders and the mechanism of action of antidepressant drugs. However, the relationship between BDNF and serotonergic signalling is poorly understood. Heterozygous mutants BDNF +/- mice were utilized to investigate the influence of BDNF on the serotonin (5-HT) system and the activity of the serotonin transporter (SERT) in the hippocampus. The zero net flux method of quantitative microdialysis revealed that BDNF +/- heterozygous mice have increased basal extracellular 5-HT levels in the hippocampus and decreased 5-HT reuptake capacity. In keeping with these results, the selective serotonin reuptake inhibitor paroxetine failed to increase hippocampal extracellular 5-HT levels in BDNF +/- mice while it produced robust effects in wild-type littermates. Using in-vitro autoradiography and synaptosome techniques, we investigated the causes of attenuated 5-HT reuptake in BDNF +/- mice. A significant decrease in [3H]citalopram-binding-site density in the CA3 subregion of the ventral hippocampus and a significant reduction in [3H]5-HT uptake in hippocampal synaptosomes, revealed mainly a decrease in SERT function. However, 5-HT1A autoreceptors were not desensitized in BDNF +/- mice. These results provide evidence that constitutive reductions in BDNF modulate SERT function reuptake in the hippocampus.

Original publication




Journal article


Int J Neuropsychopharmacol

Publication Date





79 - 92


8-Hydroxy-2-(di-n-propylamino)tetralin, Animals, Autoradiography, Brain Chemistry, Brain-Derived Neurotrophic Factor, Citalopram, Dose-Response Relationship, Drug, Electrophysiology, Hippocampus, Male, Mice, Mice, Knockout, Microdialysis, Paroxetine, Phenotype, Raphe Nuclei, Receptor, Serotonin, 5-HT1A, Serotonin, Serotonin Plasma Membrane Transport Proteins, Serotonin Receptor Agonists, Serotonin Uptake Inhibitors, Synaptic Transmission