NEUROBEHAVIORAL AND PREGNANCY EFFECTS OF PRENATAL ZIDOVUDINE EXPOSUREIN SPRAGUE-DAWLEY RATS - PRELIMINARY FINDINGS

In 1994, the Public Health Service made prenatal zidovudine (ZDV, AZT) the standard of care to prevent mother-to-child transmission of HIV. The current study was undertaken to determine if prenatal exposure to ZDV has an impact on pregnancy outcomes, birth anomalies. or offspring behavior in an animal model using Sprague-Dawley (SD) rats. Thirty-on e virgin female SD rats were mated and randomly assigned to receive ei ther ZDV at 150 mg/kg/day or vehicle via gastric intubation for 22 day s starting on gestation day (G) 1. On G 22, teratologic examination of 12 litters showed no gross structural malformations. There were no si gnificant differences between the groups for maternal food and water c onsumption or maternal weight gain across pregnancy. However, ZDV trea tment significantly reduced litter size and increased birth weights fo r both male and female pups. One developmental milestone, pinna detach ment, occurred significantly earlier in the ZDV-exposed male pups comp ared to the vehicle intubated male controls. On day 21-22 of life, pup s in each litter were injected with one of four doses of amphetamine a nd were observed for behavioral activity in a photobeam-based activity monitor for 1 h. Overall amphetamine increased activity and decreased thigmotaxis or wall-hugging behavior. ZDV treatment increased the loc omotor response to amphetamine in females only and dampened the action of amphetamine to decrease thigmotaxis in both genders. Further studi es are warranted to determine the threshold dose at which these change s occur, the duration of the effects, as well as the neurochemical sys tem(s) responsible for the altered amphetamine responses. (C) 1998 Els evier Science Inc.