Effects of chronic lithium administration on rat brain phosphatidylinositol cycle constituents, membrane phospholipids and amino acids

Objective: There is evidence linking affective disorders and their treatmen t to alterations in membrane phospholipid metabolism, the phosphatidylinosi tol (PtdIns) second messenger cycle and brain excitatory and inhibitory ami no acids. This study examines lithium effects on rat brain metabolites asso ciated with the above systems and their reversal by myo-inositol. Methods: Thirty rats were treated for 14 days with i.p. lithium, saline or lithium plus inyo-inositol. H-1, P-31 and Li-7 NMR were used to measure bra in metabolites. Results: Lithium, administered alone or with inyo-inositol, resulted in bra in lithium concentrations of approximately 0.6 muM/gram brain tissue. Brain myo-inositol was unchanged when lithium was co-administered with myo-inosi tol. Lithium increased brain inositol-1-phosphate (I1P) by 98% compared wit h saline and this effect was not attenuated by the addition of myo-inositol . Lithium treatment decreased phosphatidylserine (PtdSer) and PtdIns by 3% an d 8%. respectively. Lithium also decreased taurine levels by 8% and increas ed aspartate levels by 9%. The above effects of lithium on PtdSer, PtdIns a nd taurine were attenuated or abolished by the co-administration of myo-ino sitol. Conclusions: Lithium alters levels of key membrane phospholipids and appear s to affect the balance between inhibitory and excitatory amino acids in ra t brain. Co-administration of myo-inositol attenuates some of these lithium effects on brain metabolites.