Show simple item record

dc.contributor.authorLiu, Liwang
dc.contributor.authorZhao-Shea, Rubing
dc.contributor.authorMcIntosh, J. Michael
dc.contributor.authorTapper, Andrew R.
dc.date2022-08-11T08:08:29.000
dc.date.accessioned2022-08-23T15:57:11Z
dc.date.available2022-08-23T15:57:11Z
dc.date.issued2013-10-15
dc.date.submitted2014-05-13
dc.identifier.citation<p>Liu L, Zhao-Shea R, McIntosh JM, Tapper AR. Nicotinic acetylcholine receptors containing the α6 subunit contribute to ethanol activation of ventral tegmental area dopaminergic neurons. Biochem Pharmacol. 2013 Oct 15;86(8):1194-200. doi:10.1016/j.bcp.2013.06.015. <a href="http://dx.doi.org/10.1016/j.bcp.2013.06.015">Link to article on publisher's site</a></p>
dc.identifier.issn0006-2952 (Linking)
dc.identifier.doi10.1016/j.bcp.2013.06.015
dc.identifier.pmid23811312
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30138
dc.description.abstractNicotine and alcohol are often co-abused suggesting a common mechanism of action may underlie their reinforcing properties. Both drugs acutely increase activity of ventral tegmental area (VTA) dopaminergic (DAergic) neurons, a phenomenon associated with reward behavior. Recent evidence indicates that nicotinic acetylcholine receptors (nAChRs), ligand-gated cation channels activated by ACh and nicotine, may contribute to ethanol-mediated activation of VTA DAergic neurons although the nAChR subtype(s) involved has not been fully elucidated. Here we show that expression and activation of nAChRs containing the alpha6 subunit contribute to ethanol-induced activation of VTA DAergic neurons. In wild-type (WT) mouse midbrain sections that contain the VTA, ethanol (50 or 100 mM) significantly increased firing frequency of DAergic neurons. In contrast, ethanol did not significantly increase activity of VTA DAergic neurons in mice that do not express CHRNA6, the gene encoding the alpha6 nAChR subunit (alpha6 knock-out (KO) mice). Ethanol-induced activity in WT slices was also reduced by pre-application of the alpha6 subtype-selective nAChR antagonist, alpha-conotoxin MII[E11A]. When co-applied, ethanol potentiated the response to ACh in WT DAergic neurons; whereas co-application of ACh and ethanol failed to significantly increase activity of DAergic neurons in alpha6 KO slices. Finally, pre-application of alpha-conotoxin MII[E11A] in WT slices reduced ethanol potentiation of ACh responses. Together our data indicate that alpha6-subunit containing nAChRs may contribute to ethanol activation of VTA DAergic neurons. These receptors are predominantly expressed in DAergic neurons and known to be critical for nicotine reinforcement, providing a potential common therapeutic molecular target to reduce nicotine and alcohol co-abuse.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23811312&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttp://dx.doi.org/10.1016/j.bcp.2013.06.015
dc.subjectAnimals
dc.subjectDopamine
dc.subjectDopaminergic Neurons
dc.subjectEthanol
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectProtein Subunits
dc.subjectReceptors, Nicotinic
dc.subjectVentral Tegmental Area
dc.subjectChemical and Pharmacologic Phenomena
dc.subjectNeuroscience and Neurobiology
dc.subjectPharmacology, Toxicology and Environmental Health
dc.subjectPsychiatry
dc.titleNicotinic acetylcholine receptors containing the alpha6 subunit contribute to ethanol activation of ventral tegmental area dopaminergic neurons
dc.typeJournal Article
dc.source.journaltitleBiochemical pharmacology
dc.source.volume86
dc.source.issue8
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/377
dc.identifier.contextkey5574356
html.description.abstract<p>Nicotine and alcohol are often co-abused suggesting a common mechanism of action may underlie their reinforcing properties. Both drugs acutely increase activity of ventral tegmental area (VTA) dopaminergic (DAergic) neurons, a phenomenon associated with reward behavior. Recent evidence indicates that nicotinic acetylcholine receptors (nAChRs), ligand-gated cation channels activated by ACh and nicotine, may contribute to ethanol-mediated activation of VTA DAergic neurons although the nAChR subtype(s) involved has not been fully elucidated. Here we show that expression and activation of nAChRs containing the alpha6 subunit contribute to ethanol-induced activation of VTA DAergic neurons. In wild-type (WT) mouse midbrain sections that contain the VTA, ethanol (50 or 100 mM) significantly increased firing frequency of DAergic neurons. In contrast, ethanol did not significantly increase activity of VTA DAergic neurons in mice that do not express CHRNA6, the gene encoding the alpha6 nAChR subunit (alpha6 knock-out (KO) mice). Ethanol-induced activity in WT slices was also reduced by pre-application of the alpha6 subtype-selective nAChR antagonist, alpha-conotoxin MII[E11A]. When co-applied, ethanol potentiated the response to ACh in WT DAergic neurons; whereas co-application of ACh and ethanol failed to significantly increase activity of DAergic neurons in alpha6 KO slices. Finally, pre-application of alpha-conotoxin MII[E11A] in WT slices reduced ethanol potentiation of ACh responses. Together our data indicate that alpha6-subunit containing nAChRs may contribute to ethanol activation of VTA DAergic neurons. These receptors are predominantly expressed in DAergic neurons and known to be critical for nicotine reinforcement, providing a potential common therapeutic molecular target to reduce nicotine and alcohol co-abuse.</p>
dc.identifier.submissionpathfaculty_pubs/377
dc.contributor.departmentTapper Lab
dc.contributor.departmentBrudnick Neuropsychiatric Research Institute
dc.contributor.departmentDepartment of Psychiatry
dc.source.pages1194-200


Files in this item

Thumbnail
Name:
Publisher version

This item appears in the following Collection(s)

Show simple item record