Several previous studies reported that the action of monoamine modulators might be involved in adult hippocampal neurogenesis. Entacapone, the inhibitor of a catechol-O-methyl transferase (COMT), prevent L-DOPA from being metabolized into 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD), which hardly cross the blood brain barrier.
In this study, we investigated the effects of Entacapone on cell proliferation and neuroblast differentiation in the mouse dentate gyrus using anti-Ki67 and anti-doublecortin (DCX) antibodies. From 7 weeks of age, 50 mg/kg of Entacapone was orally administered once a day for 3 weeks. The animals were sacrificed 2 hr after the last Entacapone treatment. Entacapone markedly increased the number of Ki67-positive nuclei and DCX-immunoreactive neuroblasts compared to the vehicle (0.9% saline)-treated group. The administration of Entacapone also increased the levels of brain-derived neurotrophic factor (BDNF) in the dentate gyrus. This result suggests that Entacapone significantly promotes cell proliferation and the number of differentiating neuroblasts through an increase in BDNF levels in the mouse dentate gyrus.