ETHANOL TOLERANCE AND DEPENDENCE IN VITRO

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The overall objectives of the proposed research are to determine the acute and chronic effects of ethanol on neurotransmitter receptor function and on membrane fluidity. A clone of mouse neuroblastoma (N1E-115) which contains prostaglandin and muscarinic acetylcholine receptors and a clone of rat glioma (C-6) which contains Beta-adrenergic receptor will be used in these studies. These receptors will be assayed by pharmacological and radioligand binding techniques. Receptor-mediated cyclic AMP (prostaglandin, Beta-adrenergic receptors) and cyclic GMP (muscarinic receptor) synthesis will be used to pharmacologically study these receptors while (3H)prostaglandin E1, (3H)quinuclidinylbenzilate, and (125I)iodohydroxybenzylpindolol binding will be used for direct assay of the prostaglandin, muscarinic acetylcholine and Beta-adrenergic receptors, respectively. Our preliminary experiments showed an effect of ethanol on the function of prostaglandin and muscarinic acetylcholine receptors. In addition, after several days of exposure to ethanol, there developed a cellular tolerance to the effects of ethanol on these receptors. Some of our data may be explained by changes in membrane fluidity caused by ethanol as reported by others. Thus, fluorescence polarization techniques will be used to obtain direct evidence for an effect of ethanol on membrane fluidity of these cultured cells. The role of membrane fluidity changes in the acute and chronic effects of ethanol on neurotransmitter receptor function and in the induction of cellular tolerance to ethanol may be elucidated from these studies.