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 psychiatric and neurologic disorders continues to be well accepted despite the apparent lack of understanding regarding its mode of action at the molecular level. This lack of delineation in the mechanism of action is supported by numerous conflicting publications. Despite the lack of understanding, a role for calcium in the manifestation of lithium's action is a constant singular consensus. Intracellular ionized calcium ([Ca⁺⁺]_i) is involved in the proper functioning of cells because of its role in the second messenger pathway. It is therefore essential to evaluate the effect of lithium on intracellular calcium metabolism 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 showed a slight relative increase in serum Ca⁺⁺ that correlated well with the dose of LiCl administered to the rats. The baseline [Ca⁺⁺]_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-dependent response of [Ca⁺⁺]_i to LiCl treatment. The observation may therefore explain the variations that have been reported in [Ca⁺⁺]_i studies with respect to LiCl therapy using different doses.