Lee Ho-Joo, Ertley Renee N, Rapoport Stanley I, Bazinet Richard P, Rao Jagadeesh S
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, 9000 Rockville Pike, Bldg. 9, 1S -126, Bethesda, MD 20892, USA.
Neurochem Res. 2008 May;33(5):861-6. doi: 10.1007/s11064-007-9526-3. Epub 2007 Dec 14.
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.
据报道，对大鼠长期施用对双相情感障碍躁狂有效的情绪稳定剂，会下调大脑花生四烯酸级联反应的标志物。我们推测，用于治疗双相情感障碍抑郁和快速循环的拉莫三嗪长期施用可能也会如此。将雄性CDF大鼠每天一次胃内给予治疗相关剂量的拉莫三嗪（10mg/kg）或赋形剂，持续42天。分别使用免疫印迹和逆转录-聚合酶链反应在额叶皮质中定量磷脂酶A(2)（PLA(2)）同工型和环氧化酶（COX）的蛋白质水平以及COX-2的mRNA水平。与赋形剂处理的大鼠相比，长期使用拉莫三嗪可显著降低额叶皮质中COX-2的蛋白质和mRNA水平，而不会改变PLA(2)同工型的蛋白质水平。与该假设一致，拉莫三嗪和其他情绪稳定剂对大鼠脑中COX-2表达具有共同的下调作用，这可能部分解释了它们在双相情感障碍中的疗效。
