The INIA Imaging Core will develop and employ tools for quantifying, cross-sectionally and longitudinally, the effects of excessive alcohol exposure at macrostructural and cellular levels in animal models of alcoholism. Accordingly, we propose that a valid animal model of human chronic alcohol consumption will produce analogous brain structural modification at the neural circuit, cellular, and neuronal morphometric levels of analysis. We hypothesize that the alcohol-related brain changes modify brain reward and executive control circuits involved in the maintenance of excessive alcohol consumption (most notably, the extended amygdala) and that further alcohol exposure results in further deterioration of inhibitory processes to resist alcohol (hypothesized to axise from limbic and frontocerebellar systems damage). This core will develop methods to examine alcohol-induced brain changes at in vivo structural (SRI and Stanford) and in vitro cellular and molecular (Indiana and Scripps) levels of analysis. In vivo neuroimaging component will develop magnetic resonance imaging (MRI) acquisition and analysis approaches for the in vivo study of brain tissue macrostructure, microstructure, and chemical composition of brain tissue. This component will develop an in vivo animal model of alcohol-induced brain changes detectable with MRI in rats bred at the Indiana Alcohol Center to drink alcohol (P); develop acquisition and analysis approaches for MR spectroscopy (MRS), MR spectroscopic imaging (MRSI), and diffusion tensor imaging (DTI) in the in vivo study of brain tissue microstructure and chemical composition of brain tissue in rats; and create tools for interested INIA sites to collect and analyze MR neuroimaging data. Cellular imaging component will provide economically efficient facilities for conducting in vitro imaging, analysis using quantitative autoradiography, carrying out in situ hybridization, performing immunocytochemical for c-fos activation and neuroanatomical identification of neurons, microdissecting discrete CNS regions, developing laser capture microdissection techniques, and initiating studies for undertaking in vivo imaging in the alcohol animal model. Neuronal quantification component will apply stereological neuronal quantification and morphometric analysis to brain systems identified with in vivo MR as affected by alcohol. Distribution of neurotransmitters and their receptors and transporters will also be probed using markers for neurotransmitter signal transduction and antibodies for immunocytochemistry or mRNA by in situ hybridization.
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