CaltechAUTHORS
Published November 5, 2004 | Version Supplemental Material
Journal Article Open

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

Creators

  • 1. ROR icon California Institute of Technology
  • 2. ROR icon Leipzig University
  • 3. ROR icon University of Colorado Boulder

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.

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 We thank C. Fonck, B. Cohen, S. Kwoh, N. Rodrigues-Pinguet, S. Grady, J. Wehner, and S. Malin for access to unpublished work.

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Supplemental Material - Tapper.SOM.pdf

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Additional details

Identifiers

Eprint ID
51942
Resolver ID
CaltechAUTHORS:20141119-090016448

Funding

California Tobacco-Related Disease Research Program
12RT-0245
California Tobacco-Related Disease Research Program
10FT-0174
NIH
DA-3194
NIH
DA-15663
NIH
NS- 11756
NIH
MH-49716
NIH Predoctoral Fellowship
W. M. Keck Foundation
Plum Foundation

Dates

Created
2014-11-19
Created from EPrint's datestamp field
Updated
2021-11-10
Created from EPrint's last_modified field