Rats dehydrated by 6 days of water deprivation had a low level of mitotic activity in the astrocytes ('pituicytes') of the neural lobe of the pituitary. Mitotic activity in the pituicytes was greatly increased when isotonic lithium was administered in the last 3 days of water deprivation. Rehydration on the last day of the experiment produced a further increase in mitoses. Isotonic solutions of sodium, potassium or rubidium chloride did not increase mitoses. This model of cell proliferation is of interest because the mitotic activity is related to a physiological attempt to maintain homeostasis rather than a response to injury or the development of neoplasia.

It is well established that lithium can cause morphologically visible damage to the kidneys of humans and animals. Although the clinical significance of its nephrotoxicity is debatable, it would be desirable to find a method to prevent lithium's effect on the kidneys. Toward this end, we have developed a novel method for producing nephrotoxicity that will be useful for research on prevention. A single, large, toxic dose of lithium chloride (LiCl) caused necrosis of the distal convoluted tubules, which was visible by light microscopy in 30 min, had fully developed in 1 h, and had disappeared by the next day. The lesions were seen after i.p. or i.v. injections of fasted rats of three different strains. Equivalent doses of NaCl, KCl, MgCl2 and combinations thereof had no such effect, nor did they inhibit nephrotoxicity when incorporated into the LiCl solution. However, relatively small doses of LiCl injected by any route 3 or 24 h beforehand prevented the nephrotoxicity. The mechanism of prevention is not known, but it does not involve reduction of lithium levels in the kidneys.

Lithium chloride was injected into rats by the intraperitoneal or intravenous route. The dose was proportional to body weight, in the conventional manner. Lithium levels in blood serum and organs were determined after 3-24 h. Within a given strain, large rats had higher levels than small rats. The size of the rats, and not their age, was the determining factor. The large rats had more adipose tissue than the small rats. Inasmuch as lithium distributes in body water, the excess fat in large rats reduces its volume of distribution, which may be responsible for raising the lithium levels in aqueous compartments, including serum. Male and female rats of equal body size developed equal lithium levels in serum.

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