Phencyclidine (PCP) is an important drug of abuse in the United States. The use of PCP has been increasing since 1981, especially among women of childbearing age. In the last few years it has become clear that prenatal exposure to PCP produces long-term motor and behavioral abnormalities that may be irreversible in humans. The goal of the proposed research is to establish an animal model with which to characterize the pathophysiological changes in development and behavior produced by perinatal exposure to PCP. Specific target functions will be studied based upon the known effects of prenatal exposure to PCP in humans. Both physical and behavioral development in young animals as well as behavior in adults will be investigated. The critical periods of vulnerability of the fetus and neonate to exposure to PCP will be determined. Biochemical measurements will be made in order to ascertain whether cell number or cell size is affected inthe central nervous system as a result of perinatal exposure to PCP. The integrity of the pituitary-adrenal axis will be tested as preliminary studies suggest that neonatal glucocorticoid levels are decreased as a result of prenatal exposure. The hypothesis that sexual differentiation is altered in offspring whose mothers received PCP will be tested by studying reproductive and nonreproductive sexually dimorphic behavior. The development of an animal model is essential in order to determine how prenatal exposure to PCP produces such long-term behavioral effects in humans. Knowledge of the underlying fundamental mechanisms of action by which these effects are produced is imperative in order to develop strategies with which to prevent and possibly treat the profound sequelae of prenatal exposure to this major drug of abuse.
