This application is for support to study the effects of developmental AZT exposure in a laboratory rat model. AZT is an effective antiretroviral drug with relatively low toxicity in adults. Because the CDC has proposed recently the HIV testing for all pregnant women, the detection of HIV-positive women and the use of AZT, which has been shown to reduce substantially transmission of HIV from mother to fetus, will undoubtedly increase. The Principal Investigator and her coworkers have shown that gestational AZT administration to the rat is not overtly or structurally teratogenic but does produce neurobehavioral alterations in the offspring. In the proposed experiments, they will extend these findings by determining the critical period for the effect and the threshold dose at which the neurobehavioral alterations occur. AZT will be administered to developing rats during an exposure period which is comparable to the suggested exposure period in humans. Amphetamine will be administered to exposed offspring to determine the responsiveness of the central nervous system (CNS) to a challenge drug using measures of activity. Excitatory and inhibitory processes will be examined in the offspring by quantifying the responses to acoustic startle stimuli. Offspring will be examined during the postnatal period as well as in adulthood. Plasma drug levels at the lowest observable effect dose and the distribution of labeled AZT in the fetus/pup will also be determined.
