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Chronic Administration of Lamotrigine Downregulates COX-2 mRNA and Protein in Rat Frontal Cortex

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Abstract

Chronic administration to rats of mood-stabilizers that are effective against mania in bipolar disorder, is reported to downregulate markers of the brain arachidonic acid cascade. We hypothesized that chronic administration of lamotrigine, which is used to treat depression and rapid cycling in bipolar disorder, might do so as well. Male CDF rats were administered a therapeutically relevant dose of lamotrigine (10 mg/kg) or vehicle intragastrically once daily for 42 days. Protein levels of isoforms of phospholipase A2 (PLA2) and of cyclooxygenase (COX), and the mRNA level of COX-2, were quantified in the frontal cortex using immunoblotting and RT-PCR, respectively. Compared to vehicle-treated rats, chronic lamotrigine significantly decreased frontal cortex protein and mRNA levels of COX-2 without altering protein levels of the PLA2 isoforms. Consistent with the hypothesis, lamotrigine and other mood-stabilizers have a common downregulatory action on COX-2 expression in rat brain, which may account in part for their efficacy in bipolar disorder.

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Abbreviations

COX:

Cyclooxygenase

cPLA2 :

Calcium-dependent cytosolich phospholipase A2

iPLA2 :

Calcium-independent phospholipase A2

sPLA2 :

Secretory phospholipase A2

Sn :

Stereospecifically numbered

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Acknowledgements

We thank Dr. Bjornar Hassel for his valuable comments on the study design. This work was entirely supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health.

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Authors and Affiliations

  1. Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 9000 Rockville Pike, Bldg. 9, 1S -126, Bethesda, MD, 20892, USA

    Ho-Joo Lee, Renee N. Ertley, Stanley I. Rapoport, Richard P. Bazinet & Jagadeesh S. Rao

  2. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada, M5S 3E2

    Richard P. Bazinet

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  1. Ho-Joo Lee
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  2. Renee N. Ertley
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  3. Stanley I. Rapoport
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  5. Jagadeesh S. Rao
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Correspondence to Jagadeesh S. Rao.

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Lee, HJ., Ertley, R.N., Rapoport, S.I. et al. Chronic Administration of Lamotrigine Downregulates COX-2 mRNA and Protein in Rat Frontal Cortex. Neurochem Res 33, 861–866 (2008). https://doi.org/10.1007/s11064-007-9526-3

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  • DOI: https://doi.org/10.1007/s11064-007-9526-3

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