The basic rationale for this proposed research is derived from the recent discoveries that alcohol dissolves into cell membranes, where it fluidizes and presumably disorients many of the molecules that are imbedded in the lipid bilayer. It seems reasonable to suspect that disorientation of embedded molecules would alter their normal functions. Because these functions can involve synaptic transmission, I postulate that some of the physiological and behavioral consequences of alcohol are indirect consequences of this initial molecular disorientation. One class of functionally important molecules that are embedded in the bilayer, and thus likely to be disordered, is a family of compounds known as gangliosides. The terminal end groups of gangliosides, known as sialic acids (SA), have previously been shown to be altered by alcohol, and it is thus likely that alcohol is acting on the ganglioside source of this SA. In fact, preliminary data are present herein to support this hypothesis. The proposed research will evaluate the replicability of these initial observations, and extend them to evaluate dose response, sex differences, age differences, comparisons of a single dose vs. """"""""binge"""""""" drinking, and the relationship to development of tolerance in both adults and in simulated fetal alcohol syndrome. Mechanisms whereby these effects are produced will be investigated in several ways, including determination of how acute and chronic alcohol effects might be modified by pre-treatment with gangliosides or SA precursor. Also, synthesis and degradation dynamics will be examined to help explain how the alcohol effects are occurring.
