[Biophysical membrane correlates of tolerance and dependence on alcohol]

A large number of studies have given clear indications that ethanol does affect the physicochemical properties of the membrane. Membrane reorganization and adaptation can develop against the acute disordering effect of ethanol during chronic intoxication. Nevertheless, there has been so far no direct evidence of correlations between functional tolerance or dependence and membrane physical states. Membrane physical state can be assessed by fluorescence polarization of DPH in the absence (measure of membrane 'fluidity') or presence (measured of membrane sensitivity) of ethanol added in vitro. Functional tolerance has been already correlated with a reduced synaptic membrane sensitivity to ethanol (membrane tolerance). Behavioural dependence was shown to be quantifiable by measurement of alcohol intake in a free choice situation (water/alcohol) solution). This dependence model allowed us to define a membrane dependence which consists in an increased membrane rigidity (or decrease in 'fluidity') persistent after withdrawal, and which was correlated to the intensity of the behavioural dependence. This biophysical expression of dependence seems rather independent of the biophysical membrane tolerance (resistance to the acute ethanol fluidizing effect), which was found to be rapidly reversible after withdrawal and re-induced by alcohol re-intake, requiring recent periods of current abuse to be expected.