Habenula cholinergic neurons regulate anxiety during nicotine withdrawal via nicotinic acetylcholine receptors
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Authors
Pang, XueyanLiu, Liwang
Ngolab, Jennifer
Zhao-Shea, Rubing
McIntosh, J. Michael
Gardner, Paul D.
Tapper, Andrew R.
Student Authors
Jennifer NgolabXueyan Pang
Academic Program
NeuroscienceUMass Chan Affiliations
Gardner LabTapper Lab
Graduate School of Biomedical Sciences, Program in Neuroscience
Brudnick Neuropsychiatric Research Institute
Department of Psychiatry
Document Type
Journal ArticlePublication Date
2016-08-01Keywords
AcetylcholineAnxiety
Habenula
Nicotine
Withdrawal
Neuroscience and Neurobiology
Psychiatry
Psychiatry and Psychology
Substance Abuse and Addiction
Metadata
Show full item recordAbstract
Cholinergic neurons in the medial habenula (MHb) modulate anxiety during nicotine withdrawal although the molecular neuroadaptation(s) within the MHb that induce affective behaviors during nicotine cessation is largely unknown. MHb cholinergic neurons are unique in that they robustly express neuronal nicotinic acetylcholine receptors (nAChRs), although their behavioral role as autoreceptors in these neurons has not been described. To test the hypothesis that nAChR signaling in MHb cholinergic neurons could modulate anxiety, we expressed novel "gain of function" nAChR subunits selectively in MHb cholinergic neurons of adult mice. Mice expressing these mutant nAChRs exhibited increased anxiety-like behavior that was alleviated by blockade with a nAChR antagonist. To test the hypothesis that anxiety induced by nicotine withdrawal may be mediated by increased MHb nicotinic receptor signaling, we infused nAChR subtype selective antagonists into the MHb of nicotine naive and withdrawn mice. While antagonists had little effect on nicotine naive mice, blocking alpha4beta2 or alpha6beta2, but not alpha3beta4 nAChRs in the MHb alleviated anxiety in mice undergoing nicotine withdrawal. Consistent with behavioral results, there was increased functional expression of nAChRs containing the alpha6 subunit in MHb neurons that also expressed the alpha4 subunit. Together, these data indicate that MHb cholinergic neurons regulate nicotine withdrawal-induced anxiety via increased signaling through nicotinic receptors containing the alpha6 subunit and point toward nAChRs in MHb cholinergic neurons as molecular targets for smoking cessation therapeutics.Source
Neuropharmacology. 2016 Aug;107:294-304. doi: 10.1016/j.neuropharm.2016.03.039. Link to article on publisher's siteEpub 2016 Mar 26.
DOI
10.1016/j.neuropharm.2016.03.039Permanent Link to this Item
http://hdl.handle.net/20.500.14038/46255PubMed ID
27020042Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.neuropharm.2016.03.039