Fluoxetine activates melanocyte stem cells indirectly through the epithelial 5-hydroxytryptamine (5-HT) receptor 1A/Wnt signaling to regenerate melanocytes

Preclinical and clinical studies confirm McSCs have therapeutic potential for diseases including vitiligo. This study shows fluoxetine treatment, a 5-hydroxytryptamine (5-HT) reuptake inhibitor reported to promote melanin production, is associated with McSC activation.

Using narrow-band UVB (NB-UVB) irradiation as a positive control, we found that 14-day fluoxetine treatment was associated with an increased number of epidermal melanocytes in the McSC-depletion mouse model, an effect correlated with upregulated hair follicle McSC activation 1–3 days post-treatment. Notably, at the study timepoint, unlike NB-UVB irradiation, fluoxetine treatment was associated with no oxidative stress, DNA damage, apoptosis, or inflammation in mouse skin.