Finasteride Treatment Inhibits Adult Hippocampal Neurogenesis in Male Mice

Abstract

Introduction: The 5-alpha-reductase inhibitor finasteride is used for the treatment of androgenic alopecia, benign prostate hyperplasia and prostate cancer. Besides inhibiting the conversion of testosterone to the biologically more active 5α-dihydrotestosterone, it also inhibits the production of neurosteroids. Decreased neurosteroid levels are postulated to be involved in the pathophysiology of psychiatric disorders such as depression. As neurosteroids metabolized by 5-alpha-reductase influence neural plasticity, we investigated whether finasteride treatment alters adult hippocampal neurogenesis, implicated in the pathophysiology of depression.

Methods: Male C57BL/6N mice were treated subchronically (7 days) with finasteride or vehicle. Adult neurogenesis was assessed at two different time points after treatment (day 1; day 35) using immunohistochemistry.

Results: Finasteride treatment led to a significant decrease in brain 5α-dihydrotestosterone levels and induced a reversible reduction in the number of newborn cells and young neurons in the hippocampus. 35 days after the last finasteride injection, neurogenesis had returned to normal.

Discussion: These data indicate that inhibition of 5-alpha-reductase activity by finasteride treatment influences neuronal plasticity on a structural level. These changes might contribute to the pathophysiology of depressive episodes observed after finasteride treatment.

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