INTRACELLULAR IONIZED CALCIUM AND INCREASING DOSES OF LITHIUM-CHLORIDE THERAPY IN HEALTHY SPRAGUE-DAWLEY RATS

The use of lithium salts in the prophylaxis and treatment of several p sychiatric and neurologic disorders continues to be well accepted desp ite the apparent lack of understanding regarding its mode of action at the molecular level. This lack of delineation in the mechanism of act ion is supported by numerous conflicting publications. Despite the lac k of understanding, a role for calcium in the manifestation of lithium 's action is a constant singular consensus. Intracellular ionized calc ium ([Ca++](i)) is involved in the proper functioning of cells because of its role in the second messenger pathway. It is therefore essentia l to evaluate the effect of lithium on intracellular calcium metabolis m in a well-defined system. In this study, platelets loaded with Fura- 2-Acetoxymethyl were used to evaluate the effect of intraperitoneally administered lithium chloride at 0, 2.5, 5.0, 7.5, and 10 mmol/kg body wt. on [Ca++](i). The results shelved a slight relative increase in s erum Ca++ that correlated well with the dose of LiCl administered to t he rats. The baseline [Ca2(++)](i) were comparable in the study groups , but the response to thrombin stimulation was more pronounced at LiCl doses of 2.5, 5.0, and 7.5/kg body wt, compared with control and rats treated with 10 mmol LiCl/kg body wt. This finding suggests a dose-de pendent response of [Ca++]i to LiCl treatment. The observation may the refore explain the variations that have been reported in [Ca++](i) stu dies with respect to LiCl therapy using different doses.