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Alcohol acts on multiple receptor systems including the nicotinic acetylcholine receptors (nAChRs), which are known to mediate alcohol consumption and reward. We previously reported that the preclinical drug sazetidine\u2010A, a nAChR agonist and desensitizer, reduces alcohol consumption without affecting nicotine consumption in C57BL\/6J mice. Here, we found that sazetidine\u2010A enhances the expression of alcohol aversion without affecting the expression or acquisition of conditioned alcohol reward in C57BL\/6J mice. Microinjection of sazetidine\u2010A into the ventral midbrain targeting the ventral tegmental area (VTA) reduced binge alcohol consumption, implicating this region in mediating the effects of sazetidine\u2010A. Furthermore, the sazetidine\u2010A\u2010induced reduction in alcohol consumption was mediated by non\u2010\u03b14 containing nAChRs, as sazetidine\u2010A reduced binge alcohol consumption in both \u03b14 knock\u2010out and wild\u2010type mice. Finally, we found that in mice pretreated with sazetidine\u2010A, alcohol induced\n                    <jats:italic>Fos<\/jats:italic>\n                    transcript in\n                    <jats:italic>Th<\/jats:italic>\n                    \u2010, but not\n                    <jats:italic>Gad2<\/jats:italic>\n                    \u2010expressing neurons in the VTA as measured by increased\n                    <jats:italic>Fos<\/jats:italic>\n                    transcript expression. In summary, we find that sazetidine\u2010A enhances the expression of alcohol aversion, which may underlie the reduction in alcohol consumption induced by sazetidine\u2010A. Elucidating the identity of non\u2010\u03b14 nAChRs in alcohol aversion mechanisms will provide a better understanding the complex role of nAChRs in alcohol addiction and potentially reveal novel drug targets to treat AUDs.\n                  <\/jats:p>","DOI":"10.1111\/adb.12908","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T06:26:26Z","timestamp":1587709586000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Enhancement of alcohol aversion by the nicotinic acetylcholine receptor drug sazetidine\u2010A"],"prefix":"10.1111","volume":"26","author":[{"given":"Jillienne C.","family":"Touchette","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6167-5472","authenticated-orcid":false,"given":"Janna 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