DEVELOPMENTAL TOXICITY OF LITHIUM TREATMENT AT PROPHYLACTIC LEVELS

Lithium (Li+) salts are frequently used in psychiatry and may be admin istered to women in their reproductive years. We have investigated the influence of chronic Li+ administration on rat offspring. Pregnant Wi star rats drank either tap water ad libitum or 10 mM LiCl, or were wat er restricted (paired to rats receiving LiCl) until pup weaning. Follo wing birth, pups were fostered to form five experimental groups (N = n umbers of litters): a) Control-S, stressed by water restriction (N = 2 1), b) Li+ during the prenatal and lactating periods (N = 18), c) Liduring the prenatal period only (N = 22), d) Li+ during the lactating period only (N = 15), and e) Control-NS no treatment (N = 13). Prenata l water restriction or Li+ treatment impaired the performance of the r ighting 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 d ifference was found in the time to pup earflap opening, or in the moto r coordination test. The specific effect of lithium on pups included i mpairment of the righting reflex, an increase in the number of males b orn, a reduction in body weight at weaning and a delay in the eye open ing date. The serum Li+ levels of the dams were maintained at approxim ately 0.5 mEq/1. There was an increase in serum potassium, but not sod ium, concentrations. We conclude that chronic treatment of darns with Li+ in amounts similar to those used in the prophylaxis of bipolar dis orders aggravated the delay in physical and behavioral development of pups produced by stress associated with limited water intake and handl ing.