title: Modulation of ethanol reward sensitivity by nicotinic acetylcholine receptors containing the α6 subunit.
abstract: The prevalent co-abuse of nicotine and alcohol suggests a common neural mechanism underlying the actions of the two drugs. Nicotine, the addictive component of tobacco, activates nicotinic acetylcholine receptors (nAChRs) containing the α6 subunit (α6* nAChRs) in dopaminergic (DAergic) neurons of the ventral tegmental area (VTA), a region known to be crucial for drug reward. Recent evidence suggests that ethanol may potentiate ACh activation of these receptors as well, although whether α6* nAChR expression is necessary for behavioral effects of acute ethanol exposure is unknown. We compared binge-like ethanol consumption and ethanol reward sensitivity between knockout (KO) mice that do not express chrna6 (the gene encoding the α6 nAChR subunit, the α6 KO line) and wild-type (WT) littermates using the Drinking-in-the-Dark (DID) and Conditioned Place Preference (CPP) assay, respectively. In the DID assay, α6 KO female and male mice consumed ethanol similarly to WT mice at all concentrations tested. In the CPP assay, 2.0-g/kg and 3.0-g/kg, but not 0.5-mg/kg, ethanol conditioned a place preference in WT female and male mice, whereas only 2.0-g/kg ethanol conditioned a place preference in α6 KO mice. Acute challenge with ethanol reduced locomotor activity, an effect that developed tolerance with repeated injections, similarly between genotypes in both female and male mice. Together, these data indicate that expression of α6* nAChRs is not required for binge-like ethanol consumption and reward, but modulate sensitivity to the rewarding properties of the drug.
authors: Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01604, USA; Graduate Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: Melissa J
authors: MJ
authors: Guildford
authors: Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01604, USA.
authors: Anthony V
authors: AV
authors: Sacino
authors: Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01604, USA. Electronic address: andrew.tapper@umassmed.edu.
authors: Andrew R
authors: AR
authors: Tapper
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits / Q000172:deficiency*; D011978:Receptors, Nicotinic / Q000172:deficiency*; D012201:Reward
chemical_list: D021122:Protein Subunits; D011978:Receptors, Nicotinic; C104518:nicotinic receptor alpha6; D000431:Ethanol
keywords: Alcohol; Dopamine; Mice; Nicotinic receptor; Reward