title: The α6 nicotinic acetylcholine receptor subunit influences ethanol-induced sedation.
abstract: Alcohol and nicotine are often co-used and data from human and animals studies have demonstrated that common genes underlie responses to these two drugs. Recently, the genes that code for the subunits of the nicotinic acetylcholine receptors have been implicated as a common genetic mediator for alcohol and nicotine responses. The mammalian genes that code for the α6 and β3 subunits of the nicotinic acetylcholine receptor (Chrna6 and Chrnb3, respectively) are located adjacent to each other on human and mouse chromosome 8. These subunits have gained attention as potential regulators of drug behaviors because of their expression in the striatum where they have been shown to modulate dopamine release. Human genetic studies have shown that variation in these genes is associated with alcohol phenotypes. In the current experiments, mice lacking the Chrna6 or Chrnb3 gene were tested for three ethanol behaviors: choice ethanol consumption, ataxia, and sedation. Wildtype (WT), heterozygous (HET), and knockout (KO) mice of each strain went through a standard 2-bottle choice drinking paradigm, the balance beam, and the Loss of Righting Reflex (LORR) paradigm. No genotypic effects on any of the 3 behavioral tasks were observed in Chrnb3 animals. While the Chrna6 gene did not significantly influence ethanol consumption (g/kg) or ataxia, mice lacking the α6 subunit took significantly longer to recover their righting reflex than WT animals. These data provide evidence that receptors containing this subunit modulate the sedative effects of ethanol. Further work examining other models of ethanol consumption and behavioral responses to ethanol is needed to fully characterize the role of these receptor subunits in modulating ethanol responses.
authors.affiliation: Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80303, USA.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Kamens
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Hoft
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Cox
authors.forename: Jill H
authors.initials: JH
authors.lastname: Miyamoto
authors.forename: Marissa A
authors.initials: MA
authors.lastname: Ehringer
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D057897:Reflex, Righting / Q000235:genetics
chemical_list: D006993:Hypnotics and Sedatives; D011978:Receptors, Nicotinic; C104518:nicotinic receptor alpha6; D000431:Ethanol