Lithium-induced decrease of brain inositol and increase of brain inositol-1-phosphate is transient.
The effects of a single dose of LiCl (2.5 or 10 mEq/kg) on brain inositol and inositol-1-phosphate (Ins1P), intermediates of brain phosphoinositide (PI) turnover, were determined in male Han: Wistar rats. There was a remarkable, 36-58 fold elevation of brain Li+ as the single dose of LiCl was increased 4-fold. Moreover, the accumulation of brain lithium was slow during repeated administration of LiCl. Brain lithium did not correlate with changes in brain PI turnover either after a single or repeated doses. Thus, after a single dose of LiCl the increases in brain Ins1P were much less than the decreases in brain inositol. Also, brain inositol was significantly decreased only with the high dose of LiCl whereas brain Ins1P accumulation was more prominent with the lower dose. Moreover, repeated daily doses of LiCl only transiently increased brain Ins1P at 1 and 7 d whereas inositol remained at control levels throughout the 14 d observation period. Lithium probably caused the transient decrease in brain inositol by inhibiting several enzymes, in addition to the inhibition of myo-inositol mono-phosphates, in the PI cycle. Moreover, a slow dampening down of PI turnover by lithium, possible via an inhibitory action on G-protein-coupling, may also explain the present findings.
Hirvonen
M R
MR
National Public Health Institute, Department of Environmental Hygiene and Toxicology, Kuopio, Finland.
Savolainen
K
K
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007294:Inositol / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D008297:Male; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D002712:Chlorides; D007295:Inositol Phosphates; C002647:inositol 1-phosphate; D007294:Inositol; D008094:Lithium; D018021:Lithium Chloride