This project will examine the contributing mechanisms in prenatal cocaine and ethanol exposure. Both drugs have been shown to cause vasoconstriction of uterine vasculature as well as direct effects within the CNS. It is essential to evaluate the significance of hypoxia in fetuses exposed to drugs as a major inducer of toxicity to neurons. Pregnant rats will be exposed to a combination of cocaine and ethanol and the offspring's brains will be analyzed by immunocytochemical studies using antibodies against known indicators of cell toxicity and activity. The results will be compared to data collected from pups' brains that have been exposed to hypoxia only. The model used to separate the effects of hypoxia from other direct drug effects in fetal pups will take advantage of the differential vasoconstriction at each end of the rat uterine horn during cocaine exposure. This study proposes that intrauterine position has significance in not only the amount of drug reaching a fetus but also alters the severity of physiological changes (i.e. hypoxia) brought on by the drug. After gestational cocaine and ethanol exposure, a C-section will be performed to identify the intrauterine position of each pup. Separation of pups by amount of drug exposure and hypoxia will enable determine of whether specific drug effects of hypoxia is the more significant mechanism. We will compare the distal, more hypoxic brains with hypoxia-only brains to assess differences caused by the added drug exposure. In addition, we will assess exposed pups for susceptibility to further hypoxia at birth and monitor physiological differences after they reach adulthood.
|Mitchell, Ellen S; Snyder-Keller, Abigail (2003) c-fos and cleaved caspase-3 expression after perinatal exposure to ethanol, cocaine, or the combination of both drugs. Brain Res Dev Brain Res 147:107-17|
|Mitchell, Ellen S; Snyder-Keller, Abigail (2003) Blockade of D1 dopaminergic transmission alleviates c-fos induction and cleaved caspase-3 expression in the brains of rat pups exposed to prenatal cocaine or perinatal asphyxia. Exp Neurol 182:64-74|