85 kDa cytosolic phospholipase A2 is a target for chronic lithium in rat brain

THE mechanism by which chronic lithium exerts its therapeutic effect in bra ins of bipolar patients is not known. One possibility, suggested by our dem onstration in the rat brain, is that chronic lithium inhibits turnover of a rachidonic acid (AA) by reducing the activity of an AA-specific phospholipa se A2 (PLA2). To test this further, mRNA levels of two AA-specific PLA2s, c ytosolic PLA2 (cPLA2) type IV and intracellular PLA2 (iPLA2) type VIII, and protein level of cPLA2 were quantified in the brain of rats given lithium for 6 weeks. Chronic lithium markedly reduced brain mRNA and protein level of cPLA2, but had no effect on mRNA level of iPLA2. These results suggest t hat the final common path effect of chronic lithium administration is to re duce turnover of AA in brain by down-regulating cPLA2. (C) 1999 Lippincott Williams & Wilkins.