Olfactory stimulation with multiple odorants prevents stress-induced cognitive and psychological alterations.

Acute and chronic stress markedly affects behavior by triggering sympathetic nervous system activation and several hypothalamus-pituitary-adrenal-dependent responses. Brain regions of the limbic system are responsible for the regulation of stress response, and different reports have demonstrated that their activity can be influenced by olfactory stimuli. Here we report that, in mice exposed to acute restraint stress, olfactory stimulation employing a combination of three odorants, i.e. vanillin, limonene and green odor (trans-2-hexenal and cis-3-hexenol) decreased anxiety behavior, assessed in the elevated plus maze, and halted recognition and spatial memory deficits, as appraised in two different object recognition tasks. Of note, when applied singularly, the same odorants were unable to block the detrimental effects of stress. We also found that the multiple odorants stimulation prevented the development of depressive symptoms assessed by the sucrose splash test and forced swim test in an experimental model of depression, i.e. mice exposed to a chronic unpredictable stress paradigm, and reduced interleukin 1β levels in the prefrontal cortex of depressed mice. Collectively, our data indicate that olfactory stimulation counteracts the detrimental effects of acute and chronic stress on mood regulation and cognitive functions, thus representing a potential tool for the treatment of stress-induced disorders.