The purpose of this series of studies is to determine if the combination of prenatal cocaine exposure and prenatal protein malnutrition in the rat results in significant physical and behavioral abnormalities in the offspring. Because malnutrition does pose added risk, current models of prenatal cocaine exposure using only well-nourished rats may be underestimating the impact of cocaine on the mother and her offspring. It is our hypothesis that prenatal cocaine-exposure in concert with malnutrition has more severe consequences for brain development and function than either insult alone. Moreover, cocaine exposure may compromise the nutritional status of the fetus. Thus, a secondary hypothesis is that many of the independent effects of prenatal cocaine will resemble those of prenatal malnutrition. An animal model of prenatal cocaine exposure will be developed using a 2 x 2 design in which well-nourished and malnourished rats are administered the drug using a treatment paradigm which better parallels the timing and pattern of human cocaine abuse than existing models. Reproductive success of the experimental dams, the incidence of malformations in the offspring and their subsequent physical growth will be documented. During postnatal development and in adulthood, the behavior of the progeny will be examined using a battery of tests which have previously been established as sensitive indicators of behavioral change consequent to prenatal protein malnutrition. Finally, basic pharmacokinetic parameters of cocaine distribution in the brain and blood of malnourished and well-nourished fetuses will be investigated. Potential differences are of critical importance in understanding the severity of impact on CNS development and the behavior of the offspring. The research proposed in this application has considerable implications for humans because of the increasing use of cocaine by low-income, inner city women of child-bearing age, whose nutritional status is likely to be compromised.
