Chronic Administration of Lamotrigine Downregulates COX-2 mRNA and Protein in Rat Frontal Cortex |
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| Authors: | Ho-Joo Lee Renee N Ertley Stanley I Rapoport Richard P Bazinet Jagadeesh S Rao |
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| Institution: | (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;(2) Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada, M5S 3E2 |
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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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| Keywords: | Lamotrigine Brain Arachidonic acid cPLA2 COX-2 Bipolar disorder |
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