Modulation of ethanol reward sensitivity by nicotinic acetylcholine receptors containing the alpha6 subunit

UMMS Affiliation

Brudnick Neuropsychiatric Research Institute, Department of Psychiatry; Graduate School of Biomedical Sciences, Neuroscience Program; Tapper Lab

Publication Date


Document Type



Neuroscience and Neurobiology | Psychiatry | Substance Abuse and Addiction


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 alpha6 subunit (alpha6* 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 alpha6* 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 alpha6 nAChR subunit, the alpha6 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, alpha6 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 alpha6 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 alpha6* nAChRs is not required for binge-like ethanol consumption and reward, but modulate sensitivity to the rewarding properties of the drug.


Alcohol, Dopamine, Mice, Nicotinic receptor, Reward

DOI of Published Version



Alcohol. 2016 Dec;57:65-70. doi: 10.1016/j.alcohol.2016.08.006. Epub 2016 Oct 8. Link to article on publisher's site

Journal/Book/Conference Title

Alcohol (Fayetteville, N.Y.)


Co-author Melissa Guildford Derner is a doctoral student in the Neuroscience Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Related Resources

Link to Article in PubMed

PubMed ID