Effects of the TrkB Receptor Agonist 7,8-Dihydroxyflavone on the Serotonin System and the Genes Encoding BDNF, TrkB, and Bax in the Mouse Brain

Abstract

The TrkB neurotrophin receptor agonist 7,8-dihydroxyflavone is a potential compound for the treatment of neurodegenerative diseases and depression. We report here the first study on the effects of chronic administration of 7,8-dihydroxyflavone (2.5 and 5 mg/kg, 14 days, i.p.) on aggressive and depression-like behavior and on the level and metabolism of serotonin, and the mRNA encoding Htr1a and Htr2a serotonin receptors, brain-derived neurotrophic factor (Bdnf), its receptor TrkB, and the proapoptotic protein Bax in the cortex and hippocampus of adult C57BL/6 mice. These studies showed that the drug had no effect on any type of behavior. Administration of the low drug dose (2.5 mg/kg) had no effect on any of the study parameters, while administration of the high drug dose (5 mg/kg) decreased cortex and hippocampus levels of serotonin and its major metabolite 5-hydroxyindoleacetic acid and the index of serotonin metabolism in the hippocampus. At the same time, this agonist dose had no effect on the expression of the Htr1a, Htr2a, Bdnf, or TrkB genes in the structures studied, though the level of Bax mRNA decreased in the hippocampus. These data provide evidence that 7,8-dihydroxyflavone affects serotonin metabolism and the expression of the genes involved in apoptosis in the mouse hippocampus.