Studies in animals and humans have shown that cortical neuroplasticity can be modulated by increasing serotonin levels by administering selective serotonin reuptake inhibitors (SSRI). However, little is known about the mechanistic background, especially the contribution of intracortical inhibition and facilitation, which depend on gamma-aminobutyric acid (GABA) and glutamate. We aimed to explore the relevance of drivers of plasticity (glutamate- and GABA-dependent processes) for the effects of serotonin enhancement on tDCS-induced plasticity in healthy humans. A crossover, partially double-blinded, randomized, and sham-controlled study was conducted in 16 healthy right-handed individuals. Plasticity was induced in each of the 7 sessions via transcranial direct current stimulation (tDCS). Anodal, cathodal, and sham tDCS were applied to the left motor cortex under SSRI (20mg / 40mg citalopram) or placebo. Short-interval cortical inhibition (SICI) and intracortical facilitation (ICF) were monitored by paired-pulse transcranial magnetic stimulation for 5-6 hours after intervention. Under placebo, anodal tDCS-induced LTP-like plasticity decreased SICI and increased ICF. In contrast, cathodal tDCS-elicited LTD-like plasticity induced the opposite effect. Under 20 mg and 40 mg citalopram, anodal tDCS did not affect SICI significantly, while ICF was enhanced and prolonged. For cathodal tDCS, citalopram converted the increase of SICI and decrease of ICF into antagonistic effects, and this effect was dosage-dependent since it lasted longer under 40mg when compared to 20mg. We speculate that the main effect of acute serotonergic enhancement on tDCS-induced plasticity is the increase and prolongation of LTP-like plasticity effects, which involves mainly the glutamatergic system.