Chronic Exposure with 5‐Alpha Reductase Inhibitor Ameliorates Anxiety and Depression‐like Behaviors By Reducing Systemic Oxidative Stress in D‐galactose‐Induced Aging Male Rats

Abstract

AbstractBackgroundThe most common geriatric psychiatric disorders are anxiety and depression. The 5‐alpha reductase inhibitor (5‐ARIs), finasteride (Fin), is a standard medication used to treat benign prostatic hyperplasia (BPH), that often occurs in the elderly. However, the effects of Fin on mental health in aged population are still unclear. D‐galactose (D‐gal)‐induced aging has been recognized worldwide, as a model to mimic natural aging in rodents. Therefore, we investigated the effect of Fin on anxiety and depression‐like behaviors in D‐gal‐induced aging male rats.MethodTwenty‐male Wistar rats (8‐week‐old) were randomly divided into two groups (n = 10/group) to receive either vehicle as control or D‐gal (150 mg/kg/day via subcutaneous injection) for 18 weeks. At week 13, rats in each group were divided into two subgroups (n = 5/subgroup) in order to receive either vehicle (drinking water) or Fin (5 mg/kg/day) via oral gavage. At the end of the treatment, elevated‐plus maze (EPM), and splash test (ST) were performed for quantifying anxiety and depression‐like behaviors, while open‐field test (OFT) to determine locomotor activity. In addition, blood in each rat was collected for determining the metabolic profiles.ResultD‐gal‐treated rat showed no effect on metabolic disturbance, but increased systemic oxidative stress (Figure 1A‐C). Anxiety and depression‐like behavior were observed in D‐gal‐treated rats, as indicated by a decrease % preference index in the open arm of EPM and grooming time in ST (Figure 1D‐E). Fin‐treated control rats demonstrated hypercholesterolemia (Figure 1A‐B), and depression‐like behavior was observed (Figure 1E). Anxiety and depression‐like behaviors were attenuated in Fin‐treated D‐gal rats (Figure 1D‐E). Regarding the locomotor activity, no significant difference was found among all groups. (Figure 1F).ConclusionFIN exposure induced metabolic disturbance, and depression‐like behaviors in male rats. In contrast, Fin ameliorated anxiety and depression‐like behaviors in D‐gal‐induced aging rat, which may due to a reducing systemic oxidative stress. The findings in this study provide information for future clinical applications such as the use of Fin for therapeutic approach for anxiety/depression‐like behaviors in the elderly. However, caution is advised when using Fin in young men since it may induce depressive‐like behaviors.