We imaged neocortical layer 2/3 pyramidal cells in rat brain slices with two-photon laser scanning microscopy to investigate that spine motility can be influenced by the voltage-dependent Na(+) and Ca(2+) channel inhibitor, vinpocetine, which exhibited positive cognitive effects in human studies. Veratridine, which enhances sodium influx, was also tested on dendritic spine motility. Perfusion with vinpocetine, a derivative of vinca alkaloids, caused a substantial increase in the structural dynamics of dendritic spines measured by the changes in length or the number of new/retracted spines. In contrast, enhancement of sodium influx with veratridine failed to change spine motility. Our results indicate that the rapid changes in spine shape and size could occur, when calcium and sodium influx has been decreased by this vinca alkaloid. Spine motility induced by vinpocetine may be associated to microtubule alterations, an effect that was described for other vinca alkaloids. On the other hand, the potential of vinpocetine to enhance cognition in clinical studies suggests that the increased spine motility may be related to cognitive functions.