The effect of finasteride on the male rat brain

Abstract

Abstract Introduction 5AR (5-alpha reductase) inhibitors may have negative effects on psychosexual activity, but there is still debate. Objectives We aimed to observe the effect of 5-alpha reductase type 2 inhibition on the brain by using finasteride. Methods Eight fourteen-week-old male rats were assigned to one of three groups (Group 1 as the control group, Group 2 as the finasteride group, and Group 3 as the finasteride withdrawal group). Rats in Groups 2 and 3 were administered finasteride for 4 weeks, and then rats in Group 2 were sacrificed, whereas rats in Group 3 were sacrificed 4 weeks thereafter. RT‒PCR and western blot for brain hemisphere, and immunohistochemistry for hippocampus and VMPOA were performed to evaluate the effect of finasteride on 5-alpha reductase type 2 and c-Fos. Results Dihydrotestosterone (ng/dl) and the dihydrotestosterone to testosterone ratio (%) decreased after 1 month of finasteride administration (Group 2), but the changes were abrogated after discontinuation of the drug (Group 3). Generally, these results were generally in accordance with those from the western blot and immunohistochemistry experiments; however, western blot analysis of 5-alpha reductase type 2 remained downregulated in Group 3. ThemRNAexpression of 5AR and c-Fos did not significantly change but tended to increase during finasteride administration. Conclusions Administration of finasteride exerted an effect on the brain, including the hippocampus and VMPOA, via 5AR-2 inhibition, resulting in a decrease inc-Fos protein activation, which may disappear after long-term cessation of the drug.