Chronic lithium and sodium valproate both decrease the concentration of myo-inositol and increase the concentration of inositol monophosphates in rat brain.
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 phosphoinositol cycle (PI-cycle), where it is an inhibitor of the enzyme converting inositol monophosphates to myo-inositol. In contrast, sodium valproate, another 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 the present study, high resolution nuclear magnetic resonance (NMR) spectroscopy was used to study the chronic effects of both lithium and sodium valproate on the concentrations of myo-inositol and inositol monophosphates in rat brain. As predicted, lithium-treated rats exhibited a significant increase in the concentration of inositol monophosphates and a significant decrease in myo-inositol concentration compared to saline-treated controls. However, 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.
O'Donnell
T
T
Department of Psychiatry, University of Alberta, Alberta, T6G 2B7, Edmonton, Canada.
Rotzinger
S
S
Nakashima
T T
TT
Hanstock
C C
CC
Ulrich
M
M
Silverstone
P H
PH
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D018021:Lithium Chloride / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008956:Models, Chemical; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D007294:Inositol; D014635:Valproic Acid; D018021:Lithium Chloride; D003913:Dextroamphetamine