Long-term effects of early-life antipsychotic drug treatment

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DESCRIPTION (provided by applicant): This application represents a submission for an AREA R15 award. These awards are intended to support research that involves undergraduates at institutions that have limited NIH funding. The purpose of this research is to begin defining the long-term behavioral effects of early-life exposure to antipsychotic drugs (APDs). Over the past 15 years, the use of APDs in pediatric populations has doubled - a phenomenon that has garnered considerable attention in the scientific community and national media. This increase has occurred in the relative absence of basic research documenting the effects of early-life APD exposure on later brain and behavioral function. Studies of APD action in laboratory rats would serve as a significant first step in filling this void. It has been well established in adult rats that continuous receptor blockade caused by long-term APD treatment leads to compensatory yet transient changes in brain dopamine function. In contrast, there is currently no body of research that has ascertained the long-term effects of APD treatment in developing rats. Our hypothesis is that, due to the timing of such treatment, early-life exposure to APDs may engender compensatory yet permanent changes in brain dopamine function that persist through adulthood. Our own preliminary research has shown that rats treated daily with the atypical APD, risperidone, from postnatal days 14 - 42 exhibit sensorimotor gating deficits and persistent locomotor hyperactivity as young adults - behaviors linked to forebrain dopamine function. Guided by these data and our hypothesis, the current application will determine if there are critical periods for the effects of early-life risperidone exposure on locomotor activity and sensorimotor gating during adulthood, and whether early-life risperidone heightens the sensitivity of these behaviors to dopamine agonists, enhances impulsivity, and disrupts forebrain dopamine release in adulthood. The proposed work would act as a foundation for the applicant to establish a program of research aimed at elucidating the effects of early-life APD treatment. In turn, this would provide researchers, policy-makers, and practitioners with critical information regarding the long-term consequences of prolonged APD treatment during development. Finally, the proposed research will be used as a vehicle to engage undergraduates in unique and integrative research experiences in psychopharmacology, developmental neuroscience, and neurochemistry. PUBLIC HEALTH RELEVANCE: The use of antipsychotic drugs in pediatric populations has doubled over the past 15 years despite the relative absence of basic research documenting the effects of such drug exposure on later brain and behavioral function. The purpose of this research is to ascertain the long-term behavioral effects of early-life exposure to antipsychotic drugs in laboratory rats. This research will provide researchers, policy-makers, and practitioners with critical information regarding the long-term consequences of prolonged antipsychotic drug treatment during development, in addition to enhancing research experiences in neuroscience among college undergraduates at Northern Kentucky University.