Nordidemnin potently inhibits inositol uptake in cultured astrocytes and dose-dependently augments lithium's proconvulsant effect in vivo

It has been suggested that inositol uptake across the cell membrane is of i mportance for maintenance of the inositol pool involved in lithium's therap eutic effect in bipolar disease and in the lithium-pilocarpine seizure test in freely moving rats (measuring the latency of a normally subconvulsive c oncentration of pilocarpine to seizure induction in the additional presence of lithium). We have tested this hypothesis by: 1)demonstrating an extreme ly high potency of nordidemnin as an inhibitor of myo-inositol uptake in pr imary cultures of mouse astrocytes; and 2) determining the dose-response co rrelation of a nordidemnin-induced decrease in the latency before appearanc e of seizures in the lithium-pilocarpine test after intracerebroventricular injection of minute samples (10 mu l) of virtually isotonic saline solutio n. J. Neurosci. Res. 60:116-121, 2000. (C) 2000 Wiley-Liss, Inc.