Finasteride withdrawal induces anxiety-like behavior and novelty avoidance in adult male rats

Finasteride, an inhibitor of the enzyme 5alpha-reductase, prescribed for benign prostatic hyperplasia and androgenetic alopecia, induces a wide variety of side effects during treatment and upon withdrawal, like sexual dysfunction and cognitive and psychological disorders, inducing the so-called post-finasteride syndrome (PFS). Here, we explored the behavioral effects of this drug in adult male rats after subchronic finasteride treatment (20 days) and at drug discontinuation (1 month). We employed multiple behavioral paradigms, including the open field test and elevated plus maze to assess locomotor activity and anxiety, and a novelty-seeking test to evaluate exploratory behavior and approach-avoidance tendencies. Our results revealed a dichotomy between immediate and delayed finasteride effects. While effects after subchronic treatment were mild, significant behavioral alterations emerged at the withdrawal. In particular, pronounced hyperactivity, decreased center exploration in the open field, and marked avoidance of novel stimuli, collectively indicating an anxiety-like behavioral phenotype, were revealed. These results, showing a picture of increased vulnerability, are in agreement with clinical reports in PFS, highlighting the relevance of our model for this condition. Moreover, the data here described strengthen the importance of monitoring patients not only during treatment but also following discontinuation of finasteride therapy.