Up‐regulation of melanin synthesis by the antidepressant fluoxetine

Fluoxetine, a member of the class of selective serotonin reuptake inhibitors, is a potent antidepressant commonly used in clinical practice. Here, we report that fluoxetine increases cellular tyrosinase ( TYR ) activity, enhances the protein levels of microphthalmia‐associated transcription factor ( MITF ), TYR and tyrosinase‐related protein‐1 ( TRP ‐1) and eventually leads to a dramatic increase in melanin production in both murine B 16 F 10 melanoma cells and normal human melanocytes ( NHMC s). In well‐characterized C 57 BL /6 mouse models, systemic application of fluoxetine increased hair pigmentation by up‐regulating hair follicular MITF , TYR , TRP ‐1 and tyrosinase‐related protein‐2 ( TRP ‐2) protein levels. Using a serotonin 1 A receptor ( SR 1 A ) antagonist and RNA interference ( RNA i) technique, we revealed that SR 1A appears to be one of the involved pathways in the fluoxetine‐induced melanogenesis in B16F10 cells. These results suggest that fluoxetine may hold a significant therapeutic potential for treating skin hypopigmentation disorders, and SR 1A may serve as a novel target in modulating melanogenesis.