Combined effects of olfactory dysfunction and chronic stress on anxiety- and depressive- like behaviors in mice

There is a close relationship between olfactory dysfunction and depression, but the underlying mechanism remains unknown. Studies have shown that olfactory deprived animal experience a higher level of stress compared with controls. In the present study, we aimed to investigate whether olfactory deprived mice would be more vulnerable to develop cognitive and emotional impairments under chronic stresses. Mice were treated with intranasal zinc sulfate infusion which resulted in a complete but reversible loss of olfactory function, and then they were treated with either chronic restraint stress (CRS) or chronic unpredictable mild stress (CUMS) for three consecutive weeks. After that, anxiety- and depressive-like behavior, as well as spatial learning and memory were measured. We found that olfactory deficit induced depressive-like behavior and impaired spatial learning and memory in mice, and the olfactory scores were significantly correlated with depressive-like behavior or the spatial learning. After CRS, olfactory deprived mice showed less anxiety- and depressive- like behaviors and better olfactory recovery than non-stressed anosmia mice. In contrast, CUMS led to increased anxiety- and depressive-like behavior and deterred the olfactory recovery. These results indicated that transient olfactory deprivation induces emotional and cognitive impairment in mice, which could be modulated by chronic stresses with a stressor intensity dependent way.