Chronic unpredictable mild stress stimulates sexually dimorphic effects on anxiety-like behavior

Many social factors and various aversive situations may induce affective disorders, like depression and anxiety-related disorders, suggesting complex relationships among stressful situations and the onset of clinical depression. Stressful factors can be replicated in experimental models of depression, as the unpredictable chronic mild stress model (UCMS) in which the animals are randomly exposed to different stressful situations. The aim of our study was to investigate the impact of a six weeks UCMS paradigm (random pattern of mild stressors twice a day) on the development of a depressive and anxiogenic phenotype in CD1 mice. Overall, at the end of the experiment, the measured parameters indicated a sexually dimorphic effect. The body weight of UCMS mice showed a mild decrease of gain weight with a significant difference between male and female since the fourth week. To measure the anxiety-like behavior we used the elevated plus maze test, demonstrating an anxiolitic effect of UCMS exposure in female (increased number of entries into the open arms) and an anxiogenic effect (decrease in the number of entries) in male. For the hedonic behavior, we performed the sucrose preference test (SPT) calculating the consumption of sucrose solution and water. The results show that UCMS treatment causes a reduction in the fluids intake (sucrose, water and total), in particular UCMS male, suggesting a less anhedonic state. No effect of UCMS were observed about the sucrose preference. Were are currently investigating the depressive profile analyzing the results from Porsolt Test. In conclusion, present results indicate that UCMS treatment may represent a good model to test the sexually dimorphic onset of affective disorders. In future studies we will investigate related neural circuits (i.e. nNOS and vasopressin systems). This research was supported by Compagnia di San Paolo (Progetto Neuroscienze) - Turin