Lithium reduces brain inositol levels by inhibiting inositol monophosp
hatase. In a previous study it was found that administration of piloca
rpine to Li-treated rats causes limbic seizure behavior which can be r
eversed by i.c.v. myo-inositol but not chiro-inositol, suggesting that
this behavior is related to inositol depletion in the PI cycle. Hypon
atremia can lower brain inositol and hypernatremia can raise brain ino
sitol. We now report that induction of low brain inositol by hyponatre
mia followed by pilocarpine did not cause limbic seizures. Induction o
f high brain inositol using hypernatremia followed by Li-pilocarpine a
dministration did not reverse limbic seizures. These data support the
concept that inositol available for PI synthesis and inositol for osmo
tic function are sequestered in different cellular pools.