Effects of ADHD therapeutic agents, methylphenidate and atomoxetine, on hippocampal neurogenesis in the adolescent mouse dentate gyrus

Abstract

Methylphenidate (MPH) and atomoxetine (ATX) are commonly used as attention-deficit/hyperactivity disorder (ADHD) therapeutic agents. In the present study, we investigated the effects of MPH and ATX on cell proliferation and neuronal differentiation in the dentate gyrus (DG) of the adolescent mouse by 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry. BrdU-positive ((+)) cells, DCX(+) cells and BrdU(+)/NeuN(+) neurons (BrdU(+) cells with NeuN immunoreaction) were easily detected in the subgranular zone (SGZ) of the DG in the vehicle-, MPH- and ATX-treated groups. Among them, only in the 10mg/kg MPH-treated group, the numbers of BrdU(+), DCX(+) and BrdU(+)/NeuN(+) cells were significantly increased compared to those in the vehicle-treated group. In addition, brain-derived neurotrophic factor (BDNF) level was significantly increased in 10mg/kg MPH-treated group, not in the other experimental groups, compared to the vehicle-treated group. These results indicate that MPH, not ATX, can enhance cell proliferation and neuroblast differentiation in the SGZ of the DG via increasing BDNF level.