Lithium suppresses ovariectomy-induced surges in plasma gonadotropins in rats

We have reported earlier that administration of lithium, the widely-used drug for the treatment of acute mania and prophylaxis of recurrent manic-depressive bipolar disorders, leads to a disruption of estrous cycle and a significant suppression of the proestrous surge of luteinizing hormone (LH) in a number of laboratory rodents. In this report we have examined the effects of this antimanic drug on plasma and pituitary levels of LH and follicle stimulating hormone (FSH) in rats following ovariectomy (OVX), an altered endocrine state in which the levels of serum LH and FSH are highly and chronically elevated. Adult OVX rats, maintained under standardized laboratory conditions (LD 12: 12; white lights on at 06.00 h, CST) were injected (ip) with lithium, 40 days post-operation, at a dosage of 3.0 and 2.0 mEq/Kg b. wt. for 3 and 7 days respectively (twice daily at 08.00 and 16.00 h). Control OVX rats received nothing or saline injections, whereas an intact control (C) received no surgical manipulation or drug injections of any kind. As expected, the levels of plasma LH and FSH in OVX (only) group showed nearly 6-fold and 75-fold increase respectively compared to those in C. Lithium injections in OVX rats for 3 and 7 days resulted in a significant reduction in plasma LH (P less than .005 and P less than .02 respectively) and FSH (P less than .001) levels when compared with those in the OVX control groups. Lithium also led to a significant reduction in the levels of pituitary LH after both 3 (P less than .02) and 7 days (P less than .02), but the levels of pituitary FSH remained unchanged. These results suggest that the pituitary gonadotropes constitute a definitive target for lithium's action, either directly or via the hypothalamus.