Beneficial effects of combined administration of fluoxetine and mitochondria-targeted antioxidant at in behavioural and molecular studies in mice model of depression

Abstract

Chronic or recurrent stress is associated with reactive oxygen species (ROS) overproduction and can lead to oxidative damage, which plays important roles in neurodegenerative diseases. Mito – TEMPO is an antioxidant targeted at mitochondria. The aim of the presented study was to assess antidepressant and antioxidant efficacy of Mito – TEMPO administered alone or with fluoxetine in mice exposed to chronic stress. The evaluation of the antidepressant-like activity was based on forced swimming test (FST) and tail suspension test (TST). In order to evaluate the antioxidant potential, the level of mRNA expression of Adora1, Ogg1, Msra, Nrf2 and Tfam in the hippocampus of mice was determined. Behavioural research data showed the antidepressant effect of fluoxetine and Mito – TEMPO administered to mice alone and in combination. The molecular research results indicate a significant impact of chronic stress on the oxidation-reduction balance and an antioxidant effect of Mito – TEMPO. The results obtained in the study suggest that Mito – TEMPO protects DNA against oxidative damage and may be beneficial in the way of cellular function improvement under the conditions of chronic stress. Adora1, Msra, Nrf2 and Tfam genes may be involved in mediating the antioxidant effect of the combined treatment with fluoxetine and Mito – TEMPO.