Both (Li 1 ) and valproic acid (VPA) are effective in treating bipolar disorder, but the pathway by which either works, and whether it is common to both drugs, is not agreed upon. We recently reported, using an in vivo fatty acid model, that Li 1 reduces the turnover rate of the second messenger arachidonic acid (AA) by 80% in brain phospholipids of the awake rat, without changing turnover rates of docosahexaenoic or palmitic acid. Reduced AA turnover was accompanied by down-regulation of gene expression and protein levels of an AA-speci®c cytosolic phospholipase A 2 (cPLA 2 ). To see if VPA had the same effect on AA turnover, we used our in vivo fatty acid model in rats chronically administered VPA (200 mg/ kg, i.p. for 30 days). Like Li 1 , VPA treatment signi®cantly decreased AA turnover within brain phospholipids (by 28± 33%), although it had no effect on cPLA 2 protein levels. Thus, both mood stabilizers, Li 1 and VPA have a common action in reducing AA turnover in brain phospholipids, albeit by different mechanisms.

(type VI) were unaffected by lithium. These and prior results indicate that lithium targets a part of the AA cascade that involves cPLA 2 and COX-2. This effect may contribute to lithium's therapeutic action in bipolar disorder.