Chronic lithium and sodium valproate both decrease the concentration of myo-inositol and increase the concentration of inositol monophosphates in ratbrain

One of the mechanisms underlying lithium's efficacy as a mood stabilizer in bipolar disorder has been proposed to be via its effects on the phosphoino sitol cycle (PI-cycle), when it is an inhibitor of thr enzyme converting in ositol monophosphates to myo-inositol. In contrast, sodium valproate, anoth er commonly used mood stabilizer, appears to have no direct effects on this enzyme and was thus believed to have a different mechanism of action. In t he present study, high resolution nuclear magnetic resonance (NMR) spectros copy was used to study the chronic effects of both lithium and sodium valpr oate on the concentrations of myo-inositol and inositol monophosphates in r at brain. As predicted, lithium-treated rats exhibited a significant increa se in the concentration of inositol monophosphates and a significant decrea se in myo-inositol concentration compared to saline-treated controls. Howev er, unexpectedly, sodium valproate administration produced exactly the same results as lithium administration. These novel findings suggest that both lithium and sodium valproate may share a common mechanism of action in the treatment of bipolar disorder via actions on the PI-cycle. (C) 2000 Elsevie r Science B.V. All rights reserved.