Nicotinic acetylcholine receptors (nAChRs) are the sites of action of nicotine and are therefore implicated in tobacco addition. Multiple studies have shown that consumption of alcohol and the use of tobacco products are positively correlated. We have hypothesized that ethanol may interact with nAChRs, thus providing a basis for the co-addiction to both nicotine and ethanol. In addition, by showing that animals bred for differential sensitivity to ethanol are also differentially sensitive to nicotine, Dr. Christopher de Fiebre has demonstrated that ethanol and nicotine sensitivities are genetically correlated. This suggests highly that common genes regulate sensitivity to these two drugs. Perhaps these common genes are those for subunits of nAChRs.
Our present project utilizes an Xenopus oocyte expression/recording system to determine if ethanol has an effect, either stimulatory or inhibitory, on the response to nicotine of specific nAChR subtypes. Pairwise combination of alpha and beta nAChR subunites produces functional nAChR subtypes with distinct agonist sensitivities. We expect different receptor subtypes to also show differential sensitivity to ethanol. A pharmacologic profile for the effects of ethanol at each receptor subtype will be generated. The demonstration that nicotine and ethanol share sites of action may begin to offer a possible explanation of a mechanism behind the co-usage of nicotine and ethanol.