Chronic valproate treatment decreases the in vivo turnover of arachidonic acid in brain phospholipids: a possible common effect of mood stabilizers

Both (Li+) and valproic acid (VPA) are effective in treating bipolar disord er, 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 ac id model, that Li+ reduces the turnover rate of the second messenger arachi donic acid (AA) by 80% in brain phospholipids of the awake rat, without cha nging turnover rates of docosahexaenoic or palmitic acid. Reduced AA turnov er was accompanied by down-regulation of gene expression and protein levels of an AA-specific cytosolic phospholipase A(2) (cPLA(2)). To see if VPA ha d the same effect on AA turnover, we used our in vivo fatty acid model in r ats chronically administered VPA (200 mg/kg, i.p. for 30 days). Like Li+, V PA treatment significantly decreased AA turnover within brain phospholipids (by 28-33%), although it had no effect on cPLA(2) protein levels. Thus, bo th mood stabilizers, Li+ and VPA have a common action in reducing AA turnov er in brain phospholipids, albeit by different mechanisms.