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It has been suggested that histamine released by an oestrogen surge at the time of implantation plays an important part in nidation of the fertilized ovum in the rat. These observations were based on findings by Shelesnyak and his coworkers that (a) administration of intraluminal histamine caused an induction of deciduomata, (b) intraluminal administration of histamine antagonists could inhibit deciduomata, (c) intraluminal administration of histamine antagonists could inhibit ovum implantation, and (d) systemic administration of histamine and histamine-releasing agents induced deciduomata (Shelesnyak 1952a, b, c, 1954; Kraicer & Shelesnyak, 1958). These workers also observed a fall in the level of the histamine content of the uterus at the time of implantation. The results of other investigators have, however, not confirmed this hypothesis (Finn & Keen, 1962; Wrenn, Bitman, Cecil & Gilliam, 1964). Tachi, Tachi & Lindner (1970) have also shown that intraluminal administration of pyrathiazine, promethazine and benadryl into the uterus ofpseudopregnant rats at dose levels reported to suppress the decidual reaction caused extensive necrosis of the endometrium. The suppression of the decidual reaction could not, therefore, be attributed to the antihistaminic action of these drugs. In this study, the possible r\l=o^\le of histamine in implantation has been investigated by studying the effect of intraluminally administered drugs which release histamine, such as Compound 48/80 and polymixin s sulphate, anti¬ histaminic drugs such as dimethindene maleate and pheniramine maleate, another pharmacologically active agent found in the uterus, 5 hydroxytryptamine, and the 5 hydroxytryptamine antagonistic drug, 1-methyl-d-lysergic acid butanolamide (ULM-491), on implantation in normal pregnant rats. These drugs were administered at different doses on Days 3 and 4 ofpregnancy. Adult female rats of proven fertility were left overnight with males and the presence of thick clumps ofspermatozoa in the early morning vaginal smear was taken to indicate Day 1 of pregnancy. These females were then left in separate cages and on Day 3 or 4 ofpregnancy, the rat was anaesthetized with ether and the uteri exposed. Intraluminal administration of the test drug was made into the uterine horn as described by Wrenn et al. (1964) with the modification that,

THE EFFECT OF INTRALUMINALLY ADMINISTERED DRUGS ON IMPLANTATION IN NORMAL PREGNANT RATS