Time-course of malaoxon-induced alterations in brain regional inositol-1-phosphate levels in convulsing and nonconvulsing rats.

The potential of a single dose of malaoxon (26.2 or 39.2 mg/kg i.p.) to produce convulsions and to increase cerebral levels of inositol-1-phosphate (Ins1P), an intermediate in phosphoinositide (PI) cycle, was followed for 1, 4, or 72 hr. The lower dose of malaoxon did not produce convulsions whereas the higher dose induced convulsions in 60% of the exposed rats. Malaoxon caused a dose-dependent, at most 2-fold, increase in brain regional Ins1P levels in nonconvulsing rats as compared to controls. At the higher dose of malaoxon, in convulsing rats, the Ins1P-levels increased 4-fold above the control Ins1P-levels. In nonconvulsing rats, the Ins1P-levels reached their maximum 1-4 hr after the administration of malaoxon, whereas in convulsing rats the levels increased for 72 hr. The results suggest that PI-signalling is associated with convulsions produced by malaoxon.