Chronic administration of lamotrigine downregulates COX-2 mRNA and protein in rat frontal cortex.
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 A(2) (PLA(2)) 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 PLA(2) 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.
Lee
Ho-Joo
HJ
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 9000 Rockville Pike, Bldg. 9, 1S -126, Bethesda, MD 20892, USA.
Ertley
Renee N
RN
Rapoport
Stanley I
SI
Bazinet
Richard P
RP
Rao
Jagadeesh S
JS
D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D005625:Frontal Lobe / Q000187:drug effects* / Q000201:enzymology; D000077213:Lamotrigine; D008297:Male; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology*
D012333:RNA, Messenger; D014227:Triazines; D051546:Cyclooxygenase 2; D000077213:Lamotrigine