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

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Abstract

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.

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Acknowledgements

The project was supported financially by a grant from the South African National Research Foundation (grant no. 45846). The authors would like to thank Mr Cor Bester and Mrs Antoinette Fick for overseeing the welfare of the animals. We would also thank Mrs. Maureen Steyn and Mrs. Sharleen Nieuwoudt for general laboratory assistance.

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  1. Division of Pharmacology, North-West University (PUK), Internal Box 16, Potchefstroom, 2520, South Africa

    Mmalebuso L. Mokoena, Brian H. Harvey, Douglas W. Oliver & Christiaan B. Brink

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  1. Mmalebuso L. Mokoena
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  2. Brian H. Harvey
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  3. Douglas W. Oliver
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  4. Christiaan B. Brink
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Correspondence to Christiaan B. Brink.

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Mokoena, M.L., Harvey, B.H., Oliver, D.W. et al. Ozone modulates the effects of imipramine on immobility in the forced swim test, and nonspecific parameters of hippocampal oxidative stress in the rat. Metab Brain Dis 25, 125–133 (2010). https://doi.org/10.1007/s11011-010-9189-7

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