Chronic Exposure of 5‐Alpha Reductase Inhibitor in Young Male Rats Induces Not Only Metabolic Disturbance, But Also Depressive‐Like Behaviors as Similar with Obese Condition

Abstract Background Finasteride (FIN), a 5‐alpha reductase inhibitor (5‐ARIs), is one of the drugs approved for the treatment of androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH). AGA has been found to be associated with obesity. Obesity and AGA themselves often co‐occurs with anxiety and depression. Nevertheless, several studies reported adverse effects of FIN on anxiety and depression, especially in young men. A previous study also reported that FIN caused anxiety and depression in male rats; however, the effects of chronic FIN exposure in young obese condition has not been investigated. Method Twenty male Wistar rats (8‐week‐old) were divided into two groups (N = 10/group) to feed with either normal diet (ND) or high‐fat diet (HFD) for 18 weeks. At week 13, rats in each dietary group were subdivided into two subgroups to treat with either vehicle as control or FIN (5 mg/kg/day) via oral gavage. At the end of the experimental protocol, the anxiety/depression‐like behaviors were measured using the Elevated‐Plus Maze (EPM) and the Splash Test (ST), while the Open‐Field Test (OFT) was examined for locomotor activity. In addition, blood in each rat was collected for determining the metabolic profiles. Result HFD‐fed rats developed obesity and hypercholesterolemia, with an increase in systemic oxidative stress (Figure 1A‐C) . Anxiety and depressive‐like behaviors were observed in vehicle‐treated HFD‐fed rats, as indicated by decreasing % preference index in the open arm of EPM and grooming time in ST (Figure 1D‐E) . FIN treated ND‐fed rats also showed depression‐like behaviors, similar to those in vehicle‐treated HFD‐fed rats (Figure 1E) . Although FIN increased plasma cholesterol levels in HFD‐fed rats, it did not aggravate anxiety and depression‐like behaviors in HFD‐fed rats. Regarding the locomotor activity, no significant difference was found among all groups. (Figure 1F) . Conclusion All of these findings suggest that FIN exposure induced metabolic disturbance, and depression‐like behaviors as similar to obesity without the aggravating effects of FIN and obesity on depressive‐like behaviors.