The overall objective of this program of research is to investigate important questions regarding the nature of chronic ethanol neurotoxicity. The effect of chronic ethanol treatment (CET) under nutritionally-controlled conditions will be investigated in the rat using neurphysiological measures to assess synaptic function. The hippocampus will be used as a model neural system to examine the characteristics and parameters of the destructive and possible compensatory alterations produced by CET. The research plan is devided into the following categories: 1) Further characterization of alterations in synaptic function in the hippocampus in response to CET. In this series extracellular field potential recording techniques will be used to assess synaptic strength, distribution and plasticity in a number of intrinsic hippocampal afferents. 2) Investigation of the commissural fibers of the hippocampus as a potentially sensitive target site of ethanol neurotoxicity. 3) The effect of CET on functional recovery following brain damage will be assessed using physiological techniques. 4) Analysis of recurrent inhibition in different hippocampal subfields after CET. 5) Plans for the development multiple neurophysiological preparations of the hippocampus to evaluate the potential mechanisms of ethanol neurotoxicity. The information derived from this animal model will serve to characterize the matrix of changes in brain produced by prolonged ethanol exposure and will add to the growing data base from which preventative and therapeutic techniques for the treatment of human alcoholism can be developed and modified.
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