The Indiana University Alcohol Research Center already had instituted a Pilot Projects Program in its first 5 years of funding which was managed by the Administrative Core. The pilot projects have encouraged investigators to join the alcohol research field, have served as a means to obtain preliminary results for R01 and R29 grant applications, and have supported work on attractive new leads. As highlights, pilot project support enabled investigators to crystallize and determine the x-ray structure of human alcohol dehydrogenase (ADH) and to determine that there are differences in the serotonergic innervation of the brains of P compared with NP rats. We wish to continue this activity as a separate research component in the next funding period. The work contemplated for this period includes: continuation of studies on neuroendocrine responses to alcohol by high and low risk individuals; single neuron recordings from the hippocampus of NP and P rats before and after ethanol; kinetic studies on the microsomal P450 ethanol oxidizing system using stop-flow kinetics; crystallization and x-ray diffraction of human aldehyde dehydrogenase (ALDH2) protein; analysis of the heritability and effect of ethanol on gastric emptying and the electrogastrogram; establishment of transgenic animal lines to study the expression of ADH in liver and extra-hepatic tissues; determination of factors that mediate and determine the intensity of the alcohol flush reaction; measurement of the levels of the protein and mRNA of several serotonin receptors in the brains of NP and P rats; and studies on the heritability of phospholipase D activity and its response to ethanol. The projects were chosen from those submitted because of their relevance to the overall aims of the Center and their relationship to support services offered by the Cores of the Center.
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