Effect of the TrkB Antagonist-7,8-Dihydroxyflavone on Mice Serotonin System

Agonist of the TrkB receptor of neurotrophins - 7,8 dihydroxyflavone is a perspective drug for the teraphy of neurodegenerative disorders and depression. In the present work an influence of the chronic treatment of the 7,8- dihydroxyflavone (2,5 and 5 mg/kg, 14 days, i.p.) on aggressive and depressive-like behavior, as well as on the level and metabolism of serotonin, mRNA level of the serotonin receptor genes Htr1a and Htr2a, brain -derived neurotropic factor (Bdnf) and its receptor Trkb genes, Bax gene coding proapoptotic protein in cortex and hippocampus of an adult C57BL/6 mice was investigated for the first time. None of these doses affected any form of behavior. Low dose of the drug (2.5 mg/kg) didn't affect any of these parameters while high dose (5 mg/kg) caused a reduction of serotonin level in cortex and hippocampus, serotonin's major metabolite- 5-hydroxyindoleacetic acid and serotonin's metabolism rate in hippocampus. At the same time this dose didn't affect the expression of the Htr1a, Htr2a, Bdnf, TrkB genes in these structures but reduced mRNA level of Bax in hippocampus. These data show the influence of the 7,8 dihydroxyflavone on the serotonin's metabolism and the expression of genes involved in apoptosis in mice hippocampus.