Effects of lithium and amphetamine on inositol metabolism in the human brain as measured by 1H and 31P MRS.
BACKGROUND
The clinical effectiveness of lithium may be due to its decreasing the intracellular concentration of myo-inositol and increasing that of its inositol monophosphate precursors, which is known as the inositol depletion hypothesis.


METHODS
Magnetic resonance spectroscopy (MRS) was used to measure the concentration of both myo-inositol (1H MRS) and phosphomonoesters (PME) [31P MRS], in healthy volunteers in a double-blind placebo-controlled study. MRS measurements were made at baseline, again on the 7th day of lithium (1200 mg, n = 10) or placebo (n = 6) administration, and again on day 8, 2 hours following oral administration of 20 mg dextroamphetamine to stimulate the phosphoinositol (PI) cycle.


RESULTS
Subjects who received lithium showed a greater increase in PME ratios in response to amphetamine administration than did placebo-treated subjects.


CONCLUSIONS
The present results support the hypothesis that lithium administration blocks the conversion of inositol monophosphates to myo-inositol, and that this effect is especially apparent following PI cycle stimulation. The effects of lithium treatment on myo-inositol in healthy volunteers in vivo are uncertain, and may have to await improvements in the ability to measure myo-inositol in the brain.
Silverstone
P H
PH
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Rotzinger
S
S
Pukhovsky
A
A
Hanstock
C C
CC
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007294:Inositol / Q000378:metabolism*; D008094:Lithium / Q000008:administration & dosage / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010759:Phosphorus Isotopes; D012016:Reference Values; D014316:Tritium
D000697:Central Nervous System Stimulants; D010759:Phosphorus Isotopes; D014316:Tritium; D007294:Inositol; D008094:Lithium; D003913:Dextroamphetamine