Inositol 1,4,5-trisphosphate accumulation in brain of lithium-treated rats.

The mechanism of action of lithium as a drug for patients with affective disorders was investigated. Three-week-old male rats were orally administered 2.7 mEq Li2CO3/kg/d for 1 or 3 wk, and phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), inositol phosphate (IP), inositol diphosphate (IP2) and inositol triphosphate (IP3) levels in brain were measured. The levels of IP were increased 1.7 and 2.4 times after 1 wk and 3 wk of lithium administration, respectively, while PI, PIP, PIP2, IP2 and IP3 levels were not altered. IP3 was further fractionated by high-performance liquid chromatography into I-1,3,4-P3 and I-1,4,5-P3. In the control rat brain, the relative percentages of I-1,3,4-P3 and I-1,4,5-P3 were 95.8 and 4.2, respectively. However, after 3 wk of lithium administration, the values were changed to 69.6 and 30.3%, respectively. This increase in the neurotransducer I-1,4,5-P3 in the brain may be relevant to the mechanism of action in the lithium treatment of patients with manic-depressive disorders.