The Effect of 5-Hydroxytryptamine on Pregnancy

Abstract

The action of 5-hydroxytryptamine (5-HT) on pregnancy in mice has been investigated. Deleterious effects have been observed at all stages. In advanced pregnancy a single dose may kill the foetuses within half an hour.The effect in early pregnancy can be antagonized by progesterone and by prolactin, as can the toxic effects of the drug on the experimental decidual reaction. In late pregnancy progesterone produces little, and prolactin no, reversal of the toxic action of 5-HT. It is suggested that in early pregnancy, 5-HT interferes with the hormonal mechanisms responsible for the maintenance of gestation, while later on its main toxic action is exerted directly on the uterine contents.Preliminary results (Poulson, Botros & Robson 1960a, b) have shown that 5-hydroxytryptamine (5-HT) has striking effects on pregnancy in mice and rabbits. The results in mice are reported in detail here, together with additional work under¬ taken to elucidate the mechanism of action. METHODSFemale mice of known fertility (having had at least one previous litter) and bred in the Animal House at Guy's Hospital Medical School were used. The first day of pregnancy was counted from the finding of the vaginal plug, which was looked for daily. 5-HT was injected in aqueous solution and the dose is expressed as that of the creatinine sulphate salt. Since preliminary experiments showed that intraperitoneal (i.p.) injection was no more effective than the subcutaneous (s.c.) route, all subsequent doses were given s.c. The drug was administered daily over different periods of pregnancy to try and determine whether it was effective before, during or after implantation, or at all these stages. In some experiments an amine oxidase inhibitor 2,2'-(^-phenylenedioxy)-di-(ethylhydrazinium (1 + )chloride) (HP 1325) was given together with 5-HT; HP 1325 was injected s.c. in aqueous solution. Pro¬ gesterone was given s.c. in oily solution, while prolactin (22-5 i.u./mg.) was given s.c.in aqueous solution, which was prepared fresh for each experiment and never stored in the refrigerator for more than 1 week.

The 5‐hydroxytryptamine Content of the Placenta and Foetus During Pregnancy in Mice

“…The levels of 5HT in the placenta and foetus after treatment of the mother with several monoamine oxidase inhibitors were measured, and found to show no significant increase above the normal levels in these tissues. Treatment with cyproheptadine, a SHT antagonist, did not delay parturition.Previous work has shown that both 5-hydroxytryptamine (5HT) and monoamine oxidase inhibitors will interrupt pregnancy in mice if administered during the early stages (Lindsay, Poulson & Robson, 1963). This action can be prevented if progesterone or prolactin is given concurrently with these drugs, which suggests that in some way luteal secretion is inhibited and that this is responsible for the interruption of pregnancy.…”

“…5HT was used as the creatinine sulphate (May & Baker), the dose administered being 40 mg/kg of the salt, subcutaneously. All assay results are given in terms of the base.The doses of monoamine oxidase inhibitors were based on those used in previous experiments on pregnancy (Poulson & Robson, 1963). Doses of iproniazid are ix terms of the phosphate, two different doses being administered.…”

“…Previous work has shown that both 5-hydroxytryptamine (5HT) and monoamine oxidase inhibitors will interrupt pregnancy in mice if administered during the early stages (Lindsay, Poulson & Robson, 1963). This action can be prevented if progesterone or prolactin is given concurrently with these drugs, which suggests that in some way luteal secretion is inhibited and that this is responsible for the interruption of pregnancy.…”

Analysis of actions of 5‐hydroxytryptamine in pregnancy

“…In the first half of pregnancy the effect occurs when the drug is given daily for several days, e.g. from the first to sixth day, and appears to be due to an interference with the hormonal mechanism responsible for the maintenance of gestation (Lindsay, Poulson & Robson, 1963).…”

“…In the first half of pregnancy the effect occurs when the drug is given daily for several days, e.g. from the first to sixth day, and appears to be due to an interference with the hormonal mechanism responsible for the maintenance of gestation (Lindsay, Poulson & Robson, 1963).In the second half of pregnancy the effect of 5-HT comes on very rapidly 718 J. M. ROBSON AND F. M. SULLIVAN and usually causes death of the foetuses within 0-5 hr following a single injection (Poulson, Botros & Robson, 1960). It seemed likely at first that this was due to a direct toxic effect of the drug on the foetus, but this was found not to be so.…”