Serotonin affects transcranial direct current-induced neuroplasticity in humans.
BACKGROUND
Modulation of the serotonergic system affects long-term potentiation (LTP) and long-term depression (LTD), the likely neurophysiologic derivates of learning and memory formation, in animals and slice preparations. Serotonin-dependent modulation of plasticity has been proposed as an underlying mechanism for depression. However, direct knowledge about the impact of serotonin on neuroplasticity in humans is missing. Here we explore the impact of the serotonin reuptake blocker citalopram on plasticity induced by transcranial direct current stimulation (tDCS) in humans in a single-blinded, placebo-controlled, randomized crossover study.


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


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


CONCLUSIONS
Serotonin has a prominent impact on neuroplasticity in humans, which is in favor for facilitatory plasticity. Taking into account serotonergic hypoactivity in depression, this might explain deficits of learning and memory formation. Moreover, the results suggest that for therapeutic brain stimulation in depression and other neuropsychiatric diseases (e.g., in neurorehabilitation), serotonergic reinforcement may enhance facilitatory aftereffects and thereby increase the efficacy of these tools.
Nitsche
Michael A
MA
Department of Clinical Neurophysiology, Georg-August-University, Robert-Koch-Strasse 40, Göttingen 37099, Germany. mnitsch1@gwdg.de
Kuo
Min-Fang
MF
Karrasch
Ralf
R
Wächter
Bettina
B
Liebetanz
David
D
Paulus
Walter
W
D000328:Adult; D015283:Citalopram / Q000494:pharmacology; D018592:Cross-Over Studies; D004558:Electric Stimulation / Q000379:methods*; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D050781:Transcranial Magnetic Stimulation
D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors