Inositol Modulates In Vivo Effects Of Lithium In Rats

Lithium inhibits inositol monophosphatase of the phosphoinositide (PI) pathway, an effect which was suggested to be responsible for lithium's therapeutic action (Berridge et al, 1982). Lithium reduced inositol levels in rat brain following some treatment regimens and supplemental inositol reversed some of lithium's effects, including seizures resulting from lithium potentiating the response to cholinergic agonists (Tricklebank et al, 1991; Kofman et al, 1993). We used EEG measurements in rats to determine the effect of inositol on seizures induced by pilocarpine (30 mg/kg, sc) following pretreatment with acute (3 mmol/kg, ip, 20 hrs) or chronic (4 weeks) lithium. Myo-inositol (0-55 mmole, icv) dose-dependently attentuated lithium plus pilocarpine seizures when an acute but not a chronic lithium treatment was used. Epi-inositol, which is not utilized for PI synthesis blocked acute lithium and pilocarpine-induced seizures in 50% of tested rats. Similarly to its effect on muscarinic agonists, lithium increased the response to DOI, a selective 5-HT2/5-TH1C (PI-linked) agonist (Williams and Jope, 1994). While R-(-)DOI (8 mg/kg, ip) alone was not convulsive, lithium plus DOI evoked seizures. In some rats tested, myo-inositol blocked the effect of lithium on DOI-induced seizures.