Outcome of pregnancy in rats chronically exposed to 1-alpha-acetylmethadol (LAAM)

Repeated oral administration of 0.2, 0.5 or 2.0 mg of LAAM per kg to mature female rats for 21 days resulted in diminished weight gain and was sufficient to induce opiate dependence. Chronic oral administration of 0.2 and 2.0 mg/kg/day to female rats before mating and throughout gestation gave rise to a population of pups which were shown to be dependent at birth by precipitated weight loss after a s.c. injection of 2.5 mg of naloxone per kg. Among the litters born to dams maintained on the 2.0 mg/kg/day dose of LAAM, there was a high incidence of stillbirths and infanticide by biological mothers or by surrogate mothers to which they were transferred within a few hours of birth. Surviving pups from this group lost weight during the next 24 hr and weighed less than controls at the time of weaning (21 days). In contrast, pups born to dams maintained on the low dose of LAAM were not cannibalized and weighed the same as or more than controls from birth until weaning. Although this group had a higher incidence of mortality during the 1st week after fostering, mortality was significantly less than for the higher dose group.