Long-Term Lithium Administration to Rats

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Abstract
Ten rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) were divided into two groups. Five rats were given lithium-containing food and five served as controls. During the first weeks the lithium content of the food was 40 mM/kg dry weight; in order to obtain a serum lithium level comparable to that used in treatment of patients, 0.7-1 mAf, the lithium content of the food had to be raised to 60 mM/kg dry weight. Within a few days with this lithium intake, the rats developed signs of intoxication, loss of weight and decrease of fluid intake. The condition was reversed by giving the rats a free choice between 0.9-percent NaCl and tap water. With this regimen a stable serum lithium concentration of 0.8 mAf was maintained for 2 months without any signs of intoxication. The lithium-treated rats drank more saline than did the controls. This extra sodium intake resulted in a 50-percent higher total fluid intake by the lithium-treated rats than by the controls. Equally large fluid intakes of the two groups were obtained by adding more sodium to the food of the control animals and less to the food of the lithium-treated rats. During the following 2 months, the mean serum lithium concentration was; 1.1 mM and no signs of intoxication occurred. The administration of extra sodium to the lithium-treated rats did not abolish the lithium-induced lowered antidiuretic response to vasopressin. The study shows that by appropriate administration of the lithium and sodium intakes it is possible to maintain rats at a serum lithium level of 0.7-1 mM for long periods of time without signs of intoxication and with the same body weight as control rats. This may be useful for studies of lithium-induced effects. By using Brattleboro rats for the experiments, it is possible to eliminate the difference in urine flow between the lithium-treated rats and the control rats.

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