Nicotinic acetylcholine receptors containing the alpha4 subunit are critical for the nicotine-induced reduction of acute voluntary ethanol consumption
UMass Chan Affiliations
Tapper LabGardner Lab
Brudnick Neuropsychiatric Research Institute
Department of Psychiatry
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2011-03-01Keywords
alcoholismethanol
nicotine
varenicline
nicotinic acetylcholine receptors
mice
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
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.Source
Channels (Austin). 2011 Mar-Apr;5(2):124-7. Epub 2011 Mar 1.
DOI
10.4161/chan.5.2.14409Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29220PubMed ID
21239887Notes
This is an addendum to: Activation of alpha4* nAChRs is necessary and sufficient for varenicline-induced reduction of alcohol consumption.
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10.4161/chan.5.2.14409