The goals of this project are to determine if maternal cocaine use produces enduring cognitive dysfunction in the offspring and, should impairment be observed, to determine the specificity of the dysfunction. Expt. 1 examines the effects of gestational exposure, using doses that model relatively heavy human cocaine use but do not produce growth retardation or terata. Positive control groups are included so that conclusions can be drawn even if cocaine-related dysfunction is not observed. If cognitive alterations are observed, the second experiment will examine the effects of lower doses during this same period of development. If cognitive effects of combined gestational and neonatal cocaine exposure to include the period of development corresponding to the third trimester in humans. Both prenatal and neonatal cocaine exposure in the rat, at the doses and routes of administration proposed here, produce enduring changes in neuronal systems implicated in learning and memory processes. The proposed research is designed to elucidate the resulting cognitive effects. The cognitive measures are designed to tap specific areas of dysfunction that result from developmental disturbances in humans. Indices of learning transfer and attentional functioning are included, as dysfunction in these areas is considered paramount in mental retardation and attention deficit hyperactivity disorder, respectively. The fact that specific cognitive functions will be assessed offers several benefits, including: (1) an enhanced ability to select sensitive cognitive tests when assessing cocaine-exposed children; and (2) a facilitation of efforts to relate any observed dysfunction to underlying neurological damage. Two aspects of the present proposal are designed to provide a first step toward attainment of this latter goal. First, the idazoxan challenge included in the test of distractibility will provide a test of underlying differences in central noradrenergic systems as well as assess a possible therapeutic strategy. Second, if enduring cognitive dysfunction is detected in these studies, a subset of the animals will be examined for functional alterations in several central neuronal systems, using the quantified deoxyglucose autoradiographic method. These analyses would permit correlation of enduring changes in particular neuronal systems with specific types of lasting cognitive dysfunction.
