James P. Rice - US grants

DESCRIPTION (provided by applicant): The purpose of this grant proposal is to further prepare the applicant for a career in alcohol related research, with a particular emphasis on fetal alcohol spectrum disorders (FASDs). The applicant will acquire novel approaches and skills to address alcohol-related effects in fetal ethanol exposed rats, adding specific behavioral and neurobiological techniques to a broad foundation of skills in behavioral neuroscience. In addition to learning these new techniques, the applicant will also be improving his communication skills by presenting the results of the proposed experiments to the scientific community via publications and conference presentations. The goal of the current proposal is to determine how exposure to moderate levels of ethanol during early development can alter voluntary ethanol consumption later in adulthood, and how reward related circuitry in the brain is involved in these changes in behavior. Although the effects of fetal ethanol exposure have been previously described in various brain regions, the nucleus accumbens and basal forebrain have not been systematically studied in moderate exposure paradigms. Similarly, previous reports have described increased drug seeking (including ethanol) in rats exposed to ethanol during development, but have not linked this behavior to any particular brain region. The purpose of this proposal is to identify a more specific association between the nucleus accumbens, the basal forebrain, and voluntary ethanol consumption, and that this association is disrupted in rats exposed to moderate levels of ethanol in utero. As part of his doctoral dissertation project, the applicant proposes to investigate the effect of ethanol exposure on measures of dendrite length and branching in nucleus accumbens core and shell medium spiny neurons in adult fetal ethanol exposed and control rats in Aim 1. The capacity of these measures of dendritic arborization and length to predict voluntary ethanol consumption will then be evaluated. In Aim 2, the applicant proposes to test whether adult fetal ethanol exposed and control rats differ with respect to self-stimulation of basal forebrain to detect sensitivity in reward processing in fetal ethanol exposed rats. By completing these Aims, the applicant will learn to draw medium spiny neurons in the nucleus accumbens, as well as specific analytical techniques to compare regression slopes for different groups. He will also learn surgical techniques in order to test intracranial self-stimulation and related operant conditioning behavioral procedures. As preliminary data suggest, it is expected that changes in nucleus accumbens will be specific to the shell sub-region, and this effect will be increased in the fetal ethanol exposed rats. It is alo expected that these rats will self-stimulate the basal forebrain more than controls. The results of these experiments will further the understanding of the long-term effects of moderate prenatal ethanol exposure, as well as provide a potential therapeutic target for future interventions aimed at alleviating the effects of FASDs. PUBLIC HEALTH RELEVANCE: Exposure to moderate levels of ethanol during gestation has been shown to result in long lasting deficits in in behavior and related central nervous system function. Although deficits in several brain regions related to social behavior and learning and memory have been identified in animals exposed to moderate levels of ethanol in utero, few have investigated these effects on brain circuitry related to reward and addiction processes. Furthermore, how these deficits in reward circuitry may impact behavior in adulthood is also poorly understood. Using a rodent model of moderate prenatal ethanol exposure, we have identified the nucleus accumbens and the basal forebrain as a brain regions of interest with respect to deficits as a result of both prenatal ethanol exposure and voluntary ethanol consumption in adulthood. The results of these experiments will lead to a better understanding of how learning and memory related to alcohol are impacted by early development insults, and provide a therapeutic target for future research and treatments.