{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:56:13Z","timestamp":1777517773713,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,1,4]],"date-time":"2016-01-04T00:00:00Z","timestamp":1451865600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Ethanol (EtOH) and nicotine abuse are 2 leading causes of preventable mortality in the world, but little is known about the pharmacological mechanisms mediating co\u2010abuse. Few studies have examined the interaction of the acute effects of EtOH and nicotine. Here, we examine the effects of nicotine administration on the duration of EtOH\u2010induced loss of righting reflex (LORR) and characterize the nature of their pharmacological interactions in C57BL\/6J mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed the effects of EtOH and nicotine and the nature of their interaction in the LORR test using isobolographic analysis after acute injection in C57BL\/6J male mice. Next, we examined the importance of receptor efficacy using nicotinic partial agonists varenicline and sazetidine. We evaluated the involvement of major nicotinic acetylcholine receptor (nAChR) subtypes using nicotinic antagonist mecamylamine and nicotinic \u03b14\u2010 and \u03b17\u2010knockout mice. The selectivity of nicotine's actions on EtOH\u2010induced LORR was examined by testing nicotine's effects on the hypnotic properties of ketamine and pentobarbital. We also assessed the development of tolerance after repeated nicotine exposure. Last, we assessed whether the effects of nicotine on EtOH\u2010induced LORR extend to hypothermia and EtOH intake in the drinking in the dark (DID) paradigm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that acute nicotine injection enhances EtOH's hypnotic effects in a synergistic manner and that receptor efficacy plays an important role in this interaction. Furthermore, tolerance developed to the enhancement of EtOH's hypnotic effects by nicotine after repeated exposure of the drug. \u03b14* and \u03b17 nAChRs seem to play an important role in nicotine\u2013EtOH interaction in the LORR test. In addition, the magnitude of EtOH\u2010induced LORR enhancement by nicotine was more pronounced in C57BL\/6J than DBA\/2J mice. Furthermore, acute nicotine enhanced ketamine and pentobarbital hypnotic effects in the mouse. Finally, nicotine enhanced EtOH\u2010induced hypothermia but decreased EtOH intake in the DID test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results demonstrate that nicotine synergistically enhances EtOH\u2010induced LORR in the mouse.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.12918","type":"journal-article","created":{"date-parts":[[2016,1,4]],"date-time":"2016-01-04T23:52:29Z","timestamp":1451951549000},"page":"62-72","source":"Crossref","is-referenced-by-count":9,"title":["Nicotine Enhances the Hypnotic and Hypothermic Effects of Alcohol in the Mouse"],"prefix":"10.1111","volume":"40","author":[{"given":"Cassandra A.","family":"Slater","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asti","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pretal P.","family":"Muldoon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Dawson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey G.","family":"Soll","sequence":"additional","affiliation":[{"name":"Brudnick Neuropsychiatric Research Institute Department of Psychiatry University of Massachusetts Medical School Worcester Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rehab","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. Ivy","family":"Carroll","sequence":"additional","affiliation":[{"name":"Center for Organic and Medicinal Chemistry Research Triangle Institute Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew R.","family":"Tapper","sequence":"additional","affiliation":[{"name":"Brudnick Neuropsychiatric Research Institute Department of Psychiatry University of Massachusetts Medical School Worcester Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael F.","family":"Miles","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew L.","family":"Banks","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill 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