MECHANISM OF LITHIUM LETHALITY IN RATS

Lithium inhibits inositol monophosphatase and thereby lowers inositol levels and raises inositol-1-phosphate levels. Many of lithium's biolo gical effects are reversible by inositol replacement. However, lethali ty caused by high dose lithium was not found to be reversible by intra cerebroventricular inositol in various dosages or schedules. Moreover, inositol-1-phosphate, given alone or in the presence of sublethal Li doses to inhibit its degradation, did not show toxic or lethal effects . Therefore inositol depletion or inositol-1-phosphate accumulation ar e probably not related to lithium lethality.