AbstractBackgroundFew studies have investigated psychogenic sexual dysfunction including psychogenic erectile dysfunction (pED); the effect of tadalafil on sexual behavior of male rats induced by chronic unpredictable mild stress (CUMS) remains unclear.AimThe aim was to explore the influence of CUMS on sexual behavior of male rats and the effects of tadalafil on that.MethodsAdult male rats were divided into 3 groups, including the normal group without CUMS, the model group with 6 weeks’ CUMS, and the tadalafil group with treatment of tadalafil during CUMS. CUMS consists of water deprivation, food deprivation, stroboscopic lightning, white noise, cage tilting, weeding packing, and housing 2 unfamiliar rats. The apomorphine test and vaginal smear test were conducted with the aim to screen out male rats with good erectile function and make preparation for the sexual behavior test, respectively.OutcomesAt the end of the study period, the level of anhedonia and sexual function were evaluated by the sucrose preference test, sexual behavior test, and measurement of serum testosterone, dopamine, and 5-HT.ResultsSucrose preference showed significant decrease in rats after CUMS. The intromission ratio and total intromission frequency decreased significantly, while the mount latency and ejaculation latency prolonged significantly in CUMS-induced rats when compared with normal rats. Meanwhile, the treatment of tadalafil reversed the level of anhedonia and sexual function in CUMS-induced rats. However, there were no statistical differences in the levels of serum testosterone, dopamine, and 5-HT among groups.Clinical ImplicationsThe study constructed an animal model that can provide clinical insights into the mechanism of psychogenic sexual dysfunction and supports the application of tadalafil in pED therapy.Strengths and LimitationsWe found that CUMS-induced rats exhibited anhedonia and poor sexual function that could be prevented by tadalafil administration. Future research needs to construct the standard of pED model and explore the mechanism of tadalafil on central nervous system.ConclusionTadalafil could prevent the changes of depression and poor sexual function in rats induced by CUMS, and the method of CUMS and the sexual behavior test should be used in the future for pED modeling.