Neurobehavioral effects of perinatal AZT exposure in Sprague-Dawley weaning rats

Because AZT (azidothymidine, zidovudine, ZDV) has become the standard of care for preventing HIV transmission during pregnancy, we conducted a study to assess the possible neurobehavioral effects of this drug, using a rat model. Each litter was randomly assigned to a treatment group: vehicle, AZT 50, 100, or 150 mg/kg, or no treatment. Treatments were administered once daily via gastric intubation, prenatally from gestation day (G) 19-22 and then postnatally from postnatal day (PND) 2-20, except the nontreated group, which was only weighed every 4 days. On PND21 each rat was given a single dose of amphetamine (0.25, 0.50, 0.75, or 1.0 mg/kg) or saline and placed in the Accuscan activity chamber for 1 h of data collection and video taping. Results show that all of the behaviors analyzed produced statistically significant main effects of perinatal treatment, challenge drug, and time block. For distance traveled, there was a significant three-way interaction between treatment, sex, and time block, an effect that was independent of the effects of handling and injecting the rats. That is, within the males, the AZT 150 group displayed the greatest amount of locomotion, while among the females, the AZT 50 group was the most active. Furthermore, the AZT 50 group showed significantly less margin time (wall hugging) and more grooming than the nontreated control group. However, handling contributed to these differences because they were not observed when the vehicle-intubated group was used as the control. Across all treatment groups, amphetamine increased locomotion, the duration of rearing, and sniffing, while it decreased wall hugging, grooming, and time spent quiet. Complex interactions between amphetamine dose and time block were also seen for each behavior. In summary, these data indicate that amphetamine. at the doses used in the current study, alters behavior in the rat at 21 days of age, and that perinatal AZT exposure alters behavior in a single domain, locomotion with the threshold for this effect depending on genders. (C) 1999 Elsevier Science Inc.