Neurobehavioral and pregnancy effects of prenatal zidovudine exposure in 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-one virgin female SD rats were mated and randomly assigned to receive either ZDV at 150 mg/kg/day or vehicle via gastric intubation for 22 days starting on gestation day (G) 1. On G 22, teratologic examination of 12 litters showed no gross structural malformations. There were no significant differences between the groups for maternal food and water consumption or maternal weight gain across pregnancy. However, ZDV treatment significantly reduced litter size and increased birth weights for both male and female pups. One developmental milestone, pinna detachment, occurred significantly earlier in the ZDV-exposed male pups compared to the vehicle-intubated male controls. On day 21-22 of life, pups in each litter were injected with one of four doses of amphetamine and 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 locomotor response to amphetamine in females only and dampened the action of amphetamine to decrease thigmotaxis in both genders. Further studies are warranted to determine the threshold dose at which these changes occur, the duration of the effects, as well as the neurochemical system(s) responsible for the altered amphetamine responses.
Applewhite-Black
L E
LE
Department of Obstetrics and Gynecology, State University of New York, Brooklyn 11203, USA.
Dow-Edwards
D L
DL
Minkoff
H L
HL
D000661:Amphetamine; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D015215:Zidovudine; D000661:Amphetamine