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Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization

Tapper, Andrew R. and McKinney, Sheri L. and Nashmi, Raad and Schwarz, Johannes and Deshpande, Purnima and Labarca, Cesar and Whiteaker, Paul and Marks, Michael J. and Collins, Allan C. and Lester, Henry A. (2004) Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization. Science, 306 (5698). pp. 1029-1032. ISSN 0036-8075. https://resolver.caltech.edu/CaltechAUTHORS:20141119-090016448

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Abstract

The identity of nicotinic receptor subtypes sufficient to elicit both the acute and chronic effects of nicotine dependence is unknown. We engineered mutant mice with α4 nicotinic subunits containing a single point mutation, Leu^(9′) → Ala^(9′) in the pore-forming M2 domain, rendering α4* receptors hypersensitive to nicotine. Selective activation of α4* nicotinic acetylcholine receptors with low doses of agonist recapitulates nicotine effects thought to be important in dependence, including reinforcement in response to acute nicotine administration, as well as tolerance and sensitization elicited by chronic nicotine administration. These data indicate that activation of α4* receptors is sufficient for nicotine-induced reward, tolerance, and sensitization.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.1099420 DOIArticle
http://www.sciencemag.org/content/306/5698/1029PublisherArticle
http://www.sciencemag.org/content/306/5698/1029/suppl/DC1PublisherSupporting Online Material
ORCID:
AuthorORCID
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2004 American Association for the Advancement of Science. 21 April 2004; accepted 2 September 2004. This research was supported by the California Tobacco-Related Disease Research Project (grant 12RT-0245 and fellowship 10FT-0174 to R.N.), by the NIH (grants DA-3194 and DA-15663 at Boulder, NS-11756 and MH-49716 at Caltech, and National Research Service Award to A.R.T.), and by the W. M. Keck and Plum Foundations. We thank C. Fonck, B. Cohen, S. Kwoh, N. Rodrigues-Pinguet, S. Grady, J. Wehner, and S. Malin for access to unpublished work.
Funders:
Funding AgencyGrant Number
California Tobacco-Related Disease Research Program12RT-0245
California Tobacco-Related Disease Research Program10FT-0174
NIHDA-3194
NIHDA-15663
NIHNS- 11756
NIHMH-49716
NIH Predoctoral FellowshipUNSPECIFIED
W. M. Keck FoundationUNSPECIFIED
Plum FoundationUNSPECIFIED
Issue or Number:5698
Record Number:CaltechAUTHORS:20141119-090016448
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141119-090016448
Official Citation:Tapper, A. R., McKinney, S. L., Nashmi, R., Schwarz, J., Deshpande, P., Labarca, C., . . . Lester, H. A. (2004). Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization. Science, 306(5698), 1029-1032. doi: 10.1126/science.1099420
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51942
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:19 Nov 2014 23:38
Last Modified:03 Oct 2019 07:37

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