Molecular Pharmacology, Vol 17, 52-55, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Adaptation to Ethanol-Induced Fluidization of Brain Lipid Bilayers: Cross-Tolerance and Reversibility

¹ Langley Porter Neuropsychiatric Institute and Departments of Psychiatry, Biochemistry/Biophysics and Pharmacology, University of California, San Francisco, San Francisco, California 94143

Apparent tolerance to the ability of ethanol to increase membrane lipid thermal motions or membrane fluidity of artificial membranes formed from the lipid extracts of tolerant mice synaptosomal membranes has recently been observed by us. We attempted to determine whether this apparent tolerance was correlated with tolerance to the anesthetic actions of ethanol. We, consequently, measured the ability of ethanol to "fluidize" artificial membranes prepared from the membrane lipid extracts from pentobarbital, from morphine, and from pre- and postwithdrawal ethanol-tolerant mice. Membrane fluidity was assessed by measuring the fluorescence polarization of 1,6-diphenyl-l,3,5-hexatriene incorporated into the membranes. We observed that ethanol showed cross-tolerance with pentobarbital but not with morphine. Also, after withdrawal the effects of chronic ethanol treatment were reversible. The data suggest that the change in brain membrane lipid composition responsible for the apparent tolerance to the membrane "fluidizing" effects of ethanol is related to tolerance to the anesthetic actions of ethanol.

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ACKNOWLEDGMENT We would like to acknowledge the editorial and typing assistance of Kaye Welch.