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Neurochemical Research

, Volume 33, Issue 5, pp 861–866 | Cite as

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

  • Ho-Joo Lee
  • Renee N. Ertley
  • Stanley I. Rapoport
  • Richard P. Bazinet
  • Jagadeesh S. Rao
Original Paper

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.

Keywords

Lamotrigine Brain Arachidonic acid cPLA2 COX-2 Bipolar disorder 

Abbreviations

COX

Cyclooxygenase

cPLA2

Calcium-dependent cytosolich phospholipase A2

iPLA2

Calcium-independent phospholipase A2

sPLA2

Secretory phospholipase A2

Sn

Stereospecifically numbered

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Ho-Joo Lee
    • 1
  • Renee N. Ertley
    • 1
  • Stanley I. Rapoport
    • 1
  • Richard P. Bazinet
    • 1
    • 2
  • Jagadeesh S. Rao
    • 1
  1. 1.Brain Physiology and Metabolism SectionNational Institute on Aging, National Institutes of HealthBethesdaUSA
  2. 2.Department of Nutritional Sciences, Faculty of MedicineUniversity of TorontoTorontoCanada

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