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

See allHide authors and affiliations

Science  05 Nov 2004:
Vol. 306, Issue 5698, pp. 1029-1032
DOI: 10.1126/science.1099420

You are currently viewing the abstract.

View Full Text


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, Leu9′ → Ala9′ 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.

View Full Text