Inhibition of Prolactin Release by a Thalidomide-Related Compound (CG 603)

CG 603 is a cyclic imide. Some cyclic amides like thalidomide are central nervous system depressants (1). Barbiturates block ovulation in the rat (2, 3), and recently this laboratory reported that a single injection of Na pentobarbital (Pb) at 1 pm on the day of proestrus prevented the pronounced rise in serum LH on the late afternoon of proestrus (4). Serum prolactin was elevated 30 min after the Pb injection, but the late afternoon surge of serum prolactin was blocked completely. It was of interest, therefore, to determine the effects of a single injection of CG 603 given on the early afternoon of the day of proestrus on serum prolactin levels.

Materials and Methods. Mature, 3 to 4 month old virgin female Sprague-Dawley rats (Carworth Farms, Portage, MI), weighing 210-245 g each, were housed in a temperature controlled (25±1°) and artificially illuminated (lights on from 7 am to 9 pm daily) animal room. They were given Wayne Lab Blox pellets and water ad libitum. At least two consecutive estrous cycles were followed on all rats by examining daily vaginal smears, and only rats with regular 4 or 5 day cycles were used.

Individual blood samples (.5 to 1.0 ml) were removed by heart puncture under light ether anesthesia at 12 noon on the day of proestrus. This method of blood collection was found not to alter normal serum prolactin values in rats (4). A dose of 5, 10 or 25 mg CG 603 2 /100 g body wt was injected ip in .85% NaCl at 12:30 am, and the rats were bled at 1, 2, 3 and 5 pm. Control rats were injected only with .85% NaCl. The animals were killed by guillotine immediately after the 5 pm bleeding and their pituitaries were removed and weighed.