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

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 above-mentioned 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.

Ozone modulates the effects of imipramine on immobility in the forced swim test, and nonspecific parameters of hippocampal oxidative stress in the rat.

Depression has been associated with oxidative stress. There is increased awareness of the role of environmental toxins in the development of mood disorders. Ozone, a pro-oxidant and environmental pollutant, has been noted to have central nervous system effects. We investigated the effects of acute and chronic ozone inhalation on the response of imipramine in the forced-swim test (FST) and on biomarkers of oxidative stress in rat hippocampus. Sprague Dawley rats were exposed to 0, 0.25 or 0.7 ppm ozone per inhalation 4 h daily for either 30 days (chronic) or once (acute). Animals were then injected intraperitoneally with imipramine (10 mg/kg) or saline 24, 5 and 1 h before the forced-swim test. Hippocampal superoxide accumulation and lipid peroxidation were measured. Imipramine evoked an antidepressant-like effect independent of acute or chronic ozone exposure. However, 0.7 ppm acute ozone and 0.25 ppm chronic ozone attenuated the antidepressant-like effects of imipramine. The ozone exposures also elevated hippocampal superoxide accumulation and lipid peroxidation. Importantly, imipramine reversed the lipid peroxidation induced by chronic ozone, thereby preventing cellular damage induced by oxidative stress. Ozone exposure presents a feasible model with etiological validity to investigate oxidative stress in depression and antidepressant action.