Chronic lithium and sodium valproate both decrease the concentration of myoinositol 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 myoinositol. 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 myoinositol 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 myoinositol 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 Hospital, Edmonton AB T6G 2B7, Canada.
Rotzinger
S
S
Nakashima
T T
TT
Hanstock
C C
CC
Ulrich
M
M
Silverstone
P H
PH
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003401:Creatine / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology; D019298:Glucose-6-Phosphate / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007294:Inositol / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D000697:Central Nervous System Stimulants; D007295:Inositol Phosphates; D010725:Phosphocreatine; D010767:Phosphorylcholine; D007294:Inositol; D019298:Glucose-6-Phosphate; D014635:Valproic Acid; D008094:Lithium; D003401:Creatine; D005998:Glycine; D003913:Dextroamphetamine