Lithium increases body weight of rats: relation to thymolysis

Lithium treatment of patients and laboratory animals causes increased body weight. Lithium also elevates the plasma corticosterone levels of rats. Our purpose was to correlate the gain of body weight with the effects of lithium on the thymus gland, the organ most susceptible to stress and to elevated corticosterone levels. Toward this end, it was also necessary to establish a reliable and reproducible model by use of an inbred strain of rats. Female rats of the inbred Lewis strain were injected subcutaneously with lithium chloride or saline for an 18-day period. Necropsies were performed one day after the last treatment or at intervals during the treatment period. Lithium increased body weight gain compared to controls in all the experiments on Lewis rats. Contrary to the body as a whole, lithium caused loss of weight of the thymus gland. The spleen lost less weight than the thymus. Both lithium and nonspecific stress elevate plasma corticosterone and cause thymolysis. Mild nonspecific stress is known to cause increased weight gain in rats as well as in humans. Our data suggest that lithium acts like nonspecific stress to increase weight gain as a consequence of elevated glucocorticoids, manifested in our experiments by thymolysis. This mechanism has not been proposed previously.