LITHIUM DECREASES TURNOVER OF ARACHIDONATE IN SEVERAL BRAIN PHOSPHOLIPIDS

In vivo rates of incorporation and turnover of palmitate and arachidon ate in brain phospholipids were measured in awake rats treated chronic ally with lithium, following intravenous infusion of radiolabeled palm itate and arachidonate, respectively. Chronic lithium, at a brain leve l considered to be therapeutic in humans, decreased turnover of arachi donate within brain phosphatidylinositol, phosphatidylcholine and phos phatidylethanolamine by up to 80% (P < 0.001). In contrast, lithium ha d a minimal effect on turnover of palmitate, causing only a 26% reduct ion in turnover in phosphatidylcholine (P < 0.01). These results sugge st that a major therapeutic effect of lithium is to reduce turnover sp ecifically of arachidonate, possibly by inhibiting phospholipase A(2) involved in signal transduction. The effect may be secondary to the kn own action of lithium on the phosphoinositide cycle, by inhibiting the activity of inositol monophosphatase. (C) 1996 Elsevier Science Irela nd Ltd.