With the increase in the number of infants born to cocaine-abusing women, there has been an increased interest in the possible adverse neurologic effects of prenatal cocaine exposure. Our initial research, well as the research of others, indicates that auditory and visual impairment are sequelae of prenatal cocaine exposure. We propose to study these sequelae using neurophysiological, neuroanatomical, and neurobehavioral techniques in laboratory rats. We will characterize the effects of prenatal cocaine exposure in terms of (a) strain differences, (b) critical periods of vulnerability, and (c) dose-dependency. Experiment 1 will determine the dose-responses and thresholds for cocaine-induced toxicity on pregnancy by administering a broad range of cocaine doses to different groups of animals. The pregnant dams will be monitored for weight gain, food/water consumption, and mortality. The dams will then be sacrificed before parturition and their uteri examined for fetal implants, resorptions, live and dead pups, and the pups' malformations and weights and gender. These results will guide dose selection for Experiment 2 which will evaluate the teratogenic effect of cocaine on auditory and visual function. Auditory (inner ear) dysfunction will be evaluated neurobehaviorally (audiogenic seizures), electrophysiologically (BAEPs), and neuroanatomically (cochlear histologies). Visual dysfunction will also be evaluated electrophysiologically (ERGs) and neuroanatomically (retinal histologies). Experiment 2 will evaluate these variables as functions of dose and critical periods of vulnerability. """"""""Pair-feeding"""""""", """"""""ad libfeeding"""""""" and """"""""surrogate-fostering"""""""" control procedures will be used. Establishing and characterizing hearing and visual impairment as sequelae of prenatal cocaine exposure will advance knowledge about how cocaine can damage the fetal CNS and guide clinical assessment and management.
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