Lutein prevents corticosterone-induced depressive-like behavior in mice with the involvement of antioxidant and neuroprotective activities

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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.