Serotonin affects transcranial direct current-induced neuroplasticity in humans

Background: Modulation of the serotonergic system affects long term potentiation (LTP) as well as long term depression (LTD), the likely neurophysiological derivates of learning and memory formation, as shown in animals and slice preparations so far. However, knowledge about the impact of serotonin on neuroplasticity in humans is missing. This might be however of special importance, since many neurological patients receive serotonine reuptake inhibitors, e.g. after stroke. We aimed to explore the impact of the serotonin reuptake blocker citalopram on plasticity induced by transcranial direct current (tDCS) in humans.

Methods: In 12 healthy subjects, anodal excitability-enhancing or cathodal excitability-diminishing tDCS was applied to the motor cortex under a single dose of 20mg citalopram or placebo medication. Motor cortex excitability was monitored by single pulse transcranial magnetic stimulation (TMS) for up to the evening after the day of plasticity induction.

Results: Under placebo medication, anodal tDCS enhanced, and cathodal tDCS reduced excitability for about 60 to 120min. Citalopram enhanced and prolonged the facilitation induced by anodal tDCS, while it turned cathodal tDCS-induced inhibition into facilitation.

Conclusions: Serotonin has a prominent impact on neuroplasticity in humans, which is in favour for facilitatory plasticity. Future studies have to show if by this enhancing effect on plasticity, serotonin reuptake inhibitors are suited to improve rehabilitation results. Moreover, the results point to the fact that for therapeutic brain stimulation, e.g. by tDCS or rTMS, serotonergic reinforcement could be a tool to add to or multiply excitatory aftereffects and hereby reduce the necessary amount of physical stimulation energy.