Depression is a neuropsychiatry medical condition with high prevalence, in which the hypothalamic-pituitary-adrenal axis dysfunction has been postulated as the main cause. The
glucocorticoids can be harmful to the brain, particularly by induction of oxidative stress and glutamatergic damage, therefore
antioxidants or
neuroprotective agents could have beneficial effects.
Lutein (LUT) is a dietary xanthophyll able to arrive in the brain that has been used for
therapy of
macular degeneration. In this sense, several studies pointed beneficial effects of LUT in the brain, particularly in the hippocampus and prefrontal cortex, key regions in mood regulation. Thus, this study sought to evaluate
antidepressant-like,
antioxidant and
neuroprotective effects of LUT (0.1, 1 and 10 mg/kg) and
fluoxetine (10 mg/kg) given orally (p.o.), acute, 7 or 21 days, once a day, in combination or not with
corticosterone (20 mg/kg) in mice. After behavioral evaluation, the hippocampus, prefrontal cortex, and plasma were collected to assess the oxidative stress markers. And the neuroprotection against
glutamate was developed through prefrontal cortex and hippocampal slices. LUT and
fluoxetine in acute or subchronic treatment decreased immobility time at the dose 10 mg/kg. Furthermore,
corticosterone was effective to induce depressive-like behavior accompanied by an increase of the oxidative stress. Conversely, LUT and
fluoxetine were able to counteract the behavioral changes displayed by
corticosterone showing
antidepressant-like effect. In addition, both LUT and
fluoxetine presented
antioxidant effect in the hippocampus, prefrontal cortex and plasma of mice, and exhibited a capability to protect hippocampal and prefrontal cortex slices against glutamatergic toxicity. Our results demonstrated that LUT treatment presented an
antidepressant-like effect with the involvement of oxidative stress and neurochemical abnormalities amelioration. Therefore, LUT, widely used for
therapy of
macular degeneration emerge as a promising agent useful in the management of depression.