Nicotinic acetylcholine receptors containing the alpha4 subunit are critical for the nicotine-induced reduction of acute voluntary ethanol consumption
Brudnick Neuropsychiatric Research Institute, Department of Psychiatry; Gardner Lab; Tapper Lab
Neuroscience and Neurobiology
Recently, we investigated the molecular mechanisms of the smoking cessation drug varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist, in its ability to decrease voluntary ethanol intake in mice. Previous to our study, other labs had shown that this drug can decrease ethanol consumption and seeking in rat models of ethanol intake. Although varenicline was designed to be a high affinity partial agonist of nAChRs containing the alpha4 and beta2 subunits (designated as alpha4beta2*), at higher concentrations it can also act upon alpha3beta2*, alpha6*, alpha3beta4* and alpha7 nAChRs. Therefore, to further elucidate the nAChR subtype responsible for varenicline-induced reduction of ethanol consumption, we utilized a pharmacological approach in combination with two complimentary nAChR genetic mouse models, a knock-out line that does not express the alpha4 subunit (alpha4 KO) and another line that expresses alpha4* nAChRs hypersensitive to agonist (the Leu9'Ala line). We found that activation of alpha4* nAChRs was necessary and sufficient for varenicline-induced reduction of alcohol consumption. Consistent with this result, here we show that a more efficacious nAChR agonist, nicotine, also decreased voluntary ethanol intake, and that alpha4* nAChRs are critical for this reduction.
alcoholism, ethanol, nicotine, varenicline, nicotinic acetylcholine receptors, mice
DOI of Published Version
Channels (Austin). 2011 Mar-Apr;5(2):124-7. Epub 2011 Mar 1.
Channels (Austin, Tex.)
Hendrickson, Linzy M.; Gardner, Paul D.; and Tapper, Andrew R., "Nicotinic acetylcholine receptors containing the alpha4 subunit are critical for the nicotine-induced reduction of acute voluntary ethanol consumption" (2011). University of Massachusetts Medical School Faculty Publications. 1452.