Diminished weight of rat foetuses after treatment of pregnant rats with haloperidol.

Abstract

Summary. Daily treatment for 3 to 9 days with 3 to 12 mg/kg haloperidol (4-[4-(p-chlorophenyl) -4-hydroxypiperidino] -4' -fluorobutyrophenone) given by stomach tube to pregnant rats delays the growth of the foetuses, if treatment is started on the day of copulation (Day 0) or the day after. The delay is not seen if treatment is started on Days 4 or 7. If 3 to 9 mg/kg haloperidol is administered on Day 1 to Day 16, the young are normal in appearance at birth, but with 1 to 6 days' delay. These findings could indicate that implantation is initiated earlier than is generally accepted. The butyrophenone derivative, haloperidol (4-[4-(p-chlorophenyl)-4-hydroxypiperidino]-4'-fluorobutyrophenone), causes retarded implantation if adminis¬ tered to pregnant rats (Tuchmann-Duplessis & Mercier-Parot, 1967). The present investigation was carried out in order to detect at which stage of pregnancy haloperidol could interfere with the weight increase of the foetuses and, thus, indirectly influence the implantation process. In our experiments, rats were maintained in cages, each cage containing five mature, female, Sprague-Dawley rats and one mature male. Vaginal smears were taken from the females every morning. On the first day (Day 0) on which spermatozoa were observed in the smear, the females were placed in separate cages and randomly distributed between test groups and parallel control groups. Haloperidol (Janssen Pharmaceutical) was dissolved in distilled water and administered by stomach tube daily for 3 to 9 days in doses of 3, 6, 9 or 12 mg/kg. The exact days of drug administration are given in Table 1. Control animals were given 0-1 ml distilled water/100 g body weight. The haloperidol solution was kept at 5° C and a fresh solution was prepared every week. The female rats were killed on Day 20, the foetuses were counted and their body weight estimated to an accuracy of within 10 mg. In one series, the animals were given haloperidol from Days 1 to 16. The animals in this series were not killed, but allowed to proceed to term, and the day of delivery was noted (Table 2). The body weight of the foetuses recorded on Day 20 was less when halo¬ peridol had been administered from Day 0 or Day 1. The mean body