Long-Term Lithium Administration to Rats

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.

Comparing Oral Lithium Carbonate and Intraperitoneal Lithium Chloride Chronic Administrations on Rats’ Activity Levels

“…This suggests that toxicity was successfully avoided in both cases by the dosage selected and by the provision of supplementary sodium. Providing supple mentary sodium during chronic lithium administration has been shown to decrease lithium toxicity [18][19][20]. It has been suggested that administration of relatively high doses of lithium lowers the renal ability to conserve sodi um.…”

“…Differences in the stability of serum lithium concentrations achieved by the two methods may explain this disparity. Thomsen [18] and Thomsen and Olesen [20] have shown that rats finely adjust their sodium intake to levels that prevent lithium intoxica tion, in that increases in NaCl consumption parallel increases in serum lithium concentrations. It may then be argued that daily readings of NaCl intakes were inflated in rats administered diet lithium carbonate be cause the more stable serum lithium concentrations throughout the day achieved by this method led to more constant needs for extra sodium.…”

“…which were replenished daily. The NaCI solution was offered in order to reduce risk of intoxication with lithium [20]. Intakes of both fluids and food, and body weight were recorded at the same time daily.…”