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Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E2 concentration in rat brain

Molecular Psychiatry volume 7, pages 845–850 (2002)Cite this article

Abstract

Rats treated with lithium chloride for 6 weeks have been reported to demonstrate reduced turnover of arachidonic acid (AA) in brain phospholipids, and decreases in mRNA and protein levels, and enzyme activity, of AA-selective cytosolic phospholipase A2(cPLA2). We now report that chronic lithium administration to rats significantly reduced the brain protein level and enzyme activity of cyclooxygenase-2 (COX-2), without affecting COX-2 mRNA. Lithium also reduced the brain concentration of prostaglandin E2 (PGE2), a bioactive product of AA formed via the COX reaction. COX-1 and the Ca2+-independent iPLA2 (type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA2 and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.

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Acknowledgements

The authors wish to thank Professor Harvey Herschman for his critical review of this manuscript and Jane Bell for technical help.

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  1. F Bosetti and J Rintala: These authors contributed equally to this work

Authors and Affiliations

  1. Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA

    F Bosetti, J Rintala, R Seemann, T A Rosenberger, M A Contreras, S I Rapoport & M C Chang

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Correspondence to F Bosetti.

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Bosetti, F., Rintala, J., Seemann, R. et al. Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E2 concentration in rat brain. Mol Psychiatry 7, 845–850 (2002). https://doi.org/10.1038/sj.mp.4001111

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