Editors' ChoiceReceptors

The Molecules Behind Nicotine Addiction

Science's STKE  09 Nov 2004:
Vol. 2004, Issue 258, pp. tw406
DOI: 10.1126/stke.2582004tw406

Identification of the nicotinic acetylcholine receptor (nAChR) subtypes that are critical for nicotine dependence will provide insight into addiction mechanisms and should also help to identify potential smoking-cessation targets. Tapper et al. (see the Perspective by Hogg and Bertrand) engineered genetically modified mice in which nicotinic α4 receptors were hypersensitive to nicotine. A range of cellular assays and simple behavioral procedures showed that nicotinic activation of α4 nAChRs is sufficient to explain the development of sensitization and tolerance and also to explain the rewarding effects of nicotine.

A. R. Tapper, S. L. McKinney, R. Nashmi, J. Schwarz, P. Deshpande, C. Labarca, P. Whiteaker, M. J. Marks, A. C. Collins, H. A. Lester, Nicotine activation of α4* receptors: Sufficient for reward, tolerance, and sensitization. Science 306, 1029-1032 (2004). [Abstract] [Full Text]

R. C. Hogg, D. Bertrand, What genes tell us about nicotine addiction. Science 306, 983-985 (2004). [Summary] [Full Text]