Amphetamine & Brain Development: Third Trimester Model

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DESCRIPTION (provided by applicant): The primary intention of this proposal is to test the hypothesis that amphetamine exposure during the third trimester equivalent will lead to behavioral impairments related to hippocampal function and neuroanatomical alterations in the hippocampal formation using a rat model system. The use of amphetamine, and amphetamine-like drugs, by women of reproductive age is an issue of particular concern. There is a scarcity of literature documenting the detrimental consequences of amphetamine use during pregnancy due to various confounding variables, such as polydrug use and environmental factors. From earlier animal studies, amphetamine has been shown to be a behavioral teratogen and more recently, a limited number of reports indicate that prenatal amphetamine exposure will result in changes in neuroanatomical structures, such as the prefrontal cortex. In this proposal, a third trimester model will be used to investigate the effects of developmental amphetamine exposure on two learning and memory tasks that are linked to the functions of the hippocampal formation (SPECIFIC AIM #1), and to establish the correlations between behavioral; impairments with neuroanatomical alterations in the hippocampal formation (SPECIFIC AIM #2) using a rat model system. In rats, the period of rapid brain growth (equivalent to the third trimester in humans) occurs during early postnatal life, and it has been shown that this brain growth spurt is particularly vulnerable to neurotoxic agents. The findings of this proposal will allow a better understanding of amphetamine exposure during the most critical period of bra n development on cognitive functions and their correlations with the brain structures mediating these behaviors.