Ginkgo biloba extract (EGb761®) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment

In order to explain cognition-enhancing effects of standardized Ginkgo biloba extract (EGb761®), an increase of central monoaminergic neurotransmission has been suggested, but the underlying mechanisms have not yet been elucidated. Here, we confirm that the norepinephrine (NET), the serotonin (SERT), the dopamine (DAT) uptake transporters and MAO activity are inhibited by EGb761®in vitro, although rather high concentrations are required for inhibition of MAO-A and MAO-B activity. However, after 14 days of daily oral treatment with 100 mg/kg EGb761® only NE uptake is significantly decreased in NMRI mice, while 5-HT uptake and MAO activity are not affected. As synaptic dopamine clearance in the frontal cortex is mediated by NET, not DAT, these findings may give an explanation for the enhancement of dopaminergic neurotransmission by EGb761® seen in animal models, presumably linked to its positive effects on cognition and attention.