Developmental toxicity of lithium treatment at prophylactic levels

Lithium (Li+) salts are frequently used in psychiatry and may be administered to women in their reproductive years. We have investigated the influence of chronic Li+ administration on rat offspring. Pregnant Wistar rats drank either tap water ad libitum or 10 mM LiCl, or were water restricted (paired to rats receiving LiCl) until pup weaning. Following birth, pups were fostered to form five experimental groups (N = numbers of litters): a) Control-S, stressed by water restriction (N = 21), b) Li+ during the prenatal and lactating periods (N = 18), c) Li+ during the prenatal period only (N = 22), d) Li+ during the lactating period only (N = 15), and e) Control-NS no treatment (N = 13). Prenatal water restriction or Li+ treatment impaired the performance of the righting reflex, altered the number of males born and delayed the final date of eye opening. Postnatal water restriction or Li+ treatment of the dams reduced body growth and the date of eye opening of pups. No difference was found in the time to pup earflap opening, or in the motor coordination test. The specific effect of lithium on pups included impairment of the righting reflex, an increase in the number of males born, a reduction in body weight at weaning and a delay in the eye opening date. The serum Li+ levels of the dams were maintained at approximately 0.5 mEq/l. There was an increase in serum potassium, but not sodium, concentrations. We conclude that chronic treatment of dams with Li+ in amounts similar to those used in the prophylaxis of bipolar disorders aggravated the delay in physical and behavioral development of pups produced by stress associated with limited water intake and handling.