Effects of the serotonin antagonist amesergide on reproduction in female rats

Amesergide, a serotonin (5-HT₂) antagonist intended to treat depression, was administered orally to female CD rats (20/group) at doses of 0, 3, 10, or 30 mg/kg to evaluate effects of mating, fertility, litter size, live birth index (100 × total liveborn progeny/litter size), progeny survival, and weight gain of each litter. The treatment period extended from two weeks prior to mating through postpartum day 21 to cover possible effects of estrons cycle, mating, gestation, and postpartum events. Twenty additional female rats were given 30 mg/kg through gestation day 18, after which they received the acacia vehicle (recovery group). All females were allowed to deliver naturally and rear their progeny. On postpartum day 8, progeny in the control, 30 mg/kg and 30 mg/kg recovery groups were removed from dams for 4 h. Progeny were weighed as litters, returned to the dams for a 1-h nursing period, and then weighed again to provide an indication of milk intake. Mating and fertility, using the present study design, were not affected by treatment with amesergide. No effects were observed on litter size, live birth index, or progeny survival. In contrast, treatment with amesergide throughout gestation and lactation produced a significant dose-related depression in progeny body weight gains. However, when treatment was discontinued after day 18 of gestation (30 mg/kg recovery group), progeny body weight gains did not differ from those of the control group. When weight gain of progeny following 1 h of nursing on postpartum day 8 was examined, the offspring of the 30 mg/kg group in which treatment was continued through lactation, exhibited a significantly lower weight gain than did those from controls or the 30 mg/kg recovery group. This difference occurred in the absence of an observable change in nursing behavior amoung treatment groups. In conclusion, treatment of maternal animals with amesergide produced a reduction in progeny body weight gains. This effect was only apparent when treatment of the females continued through lactation and appeared to be due, at least in part, to a reduction in milk consumption by the progeny suggesting an alteration in milk production of the females.