The long-term objective of the research program is the understanding of the role of lipid composition in the ethanol-membrane interactions which lead to intoxication, and the changes in lipid composition in tolerancy and dependency. The project involves studies of the molecular interactions of ethanol with individual pure membrane lipids and simple mixtures of lipids in order to characterize and compare the effects of ethanol on the variety of lipid species of which membranes are composed. The rationale for this approach is the evidence that ethanol acts by dissolving into synapse membranes and changing the lipid physical properties and thus the membrane function. These studies involve measurement of fluidity and investigations of the thermotrophic properties of the lipids using fluorescence depolarization and spectrophotometry. The pure lipids to be studies are saturated and unsaturated phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines, cerebrosides and gangliosides. The interactions of barbiturates with some of these lipids will also be studied and compared with those of ethanol. The results will be interpreted in terms of the lipid changes known to occur in alcohol tolerancy and dependency, taking advantage of existing theories of general anesthesia. The significance of this research for human health is that it will provide insight into the mechanisms of alcoholism, particularly with respect to intoxication, tolerancy, and dependency, and cross reactivity with barbiturates. The results will be useful in suggesting some therapeutic measures for use during withdrawal, and may also suggest some diagnostic criteria for identifying individuals with a predisposition to alcoholism. These results will also provide some insight into mechanisms of general anesthesia.
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