Ozone exposure of Flinders Sensitive Line rats is a rodent translational model of neurobiological oxidative stress with relevance for depression and antidepressant response

Abstract

Rationale Major depression has been associated with higher levels of air pollution that in turn leads to neurodegeneration via increased oxidative stress. There is a need for suitable translational animal models to study the role of oxidative stress in depression and antidepressant action. Objective Considering the gene X environment hypothesis of depression, the present study investigated the effect of chronic ozone inhalation on depression and anxiety-related behavior, cognition, and brain markers of oxidative stress in the Flinders Sensitive Line (FSL) rat. In addition, response to the antioxidant melatonin, and the antidepressants desipramine or escitalopram, was assessed. Methods Rats were exposed to ozone (0.0 or 0.3 parts per million (ppm)) per inhalation for 4 h daily for a period of 15 days, while simultaneously receiving saline or the abovementioned drugs. Results The data indicate that chronic ozone inhalation induced memory impairment, anxiety and depression-like effects, reduced cortical and hippocampal superoxide dismutase and catalase activity, and compromised central monoamine levels similar to that noted in depression. Moreover, the behavioral and neurochemical effects of melatonin, desipramine, and escitalopram were mostly attenuated in the presence of ozone. Conclusion Thus, genetically susceptible individuals exposed to high levels of oxidative stress are at higher risk of developing mood and/or an anxiety disorders, showing greater redox imbalance and altered behavior. These animals are also more resistant to contemporary antidepressant treatment. The presented model provides robust face, construct, and predictive validity, suitable for studying neuronal oxidative stress in depression, antidepressant action and mechanisms to prevent neuronal oxidative stress.