The research outlined in this proposal will: (a) characterize further the alterations in behavioral responsivity to acute and chronic stressors observed in adult Spragu-Dawley rats that have been prenatally exposed to cocaine, and determine whether similar alterations in responsivity to acute and chronic stressors are seen using hormonal and neurochemical response measures, with particular emphasis in the latter on assessment of alterations in responsiveness of the DA systems to stress; (b) examine further the behavioral alterations seen in these offspring (with particular emphasis on conditioning deficits) to determine whether adult cocaine, exposed offspring exhibit not only deficits in reversal performance, but alterations in other behaviors that have been associated with disruption of DA terminal regions; behavioral features and processes leading to these alterations in cognitive performance will also be assessed. At this early stage in the investigation of the developmental toxicology of cocaine, such animal research is critical to confirm and extend potentially confounded clinical findings, to anticipate other potential consequences of early cocaine exposure, as well as to offer insights into the mechanisms influencing the developmental outcome of the large number of children that have been exposed prenatally to this drug of abuse.
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